Medical devices including polyisobutylene based polymers and derivatives thereof

ABSTRACT

The present invention is directed to a medical electrical lead including an insulative lead body formed, at least in part, from a polyisobutylene urethane, urea or urethane/urea copolymer. In some applications, the lead body can include at least one outer tubular insulator and/or an inner elongated member formed from a polyisobutylene urethane, urea or urethane/urea copolymer. Portions of the lead body formed form the polyisobutylene urethane, urea or urethane/urea copolymer can be either extruded or molded.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit under 35 U.S.C. §119 of U.S.Provisional Application No. 61/239,115, filed on Sep. 2, 2009, entitled“MEDICAL DEVICES INCLUDING POLYISOBUTYLENE BASED POLYMERS ANDDERIVATIVES THEREOF,” which is herein incorporated by reference in itsentirety for all purposes. Additionally, this application is acontinuation-in-part of U.S. application Ser. No. 12/784,559, filed onMay 21, 2010, entitled “POLYISOBUTYLENE URETHANE, UREA AND URETHANE/UREACOPOLYMERS AND MEDICAL LEADS CONTAINING THE SAME,” which claims thebenefit under 35 U.S.C. §119 of U.S. Provisional Application No.61/239,115, filed on Sep. 2, 2009, entitled “MEDICAL DEVICES INCLUDINGPOLYISOBUTYLENE BASED POLYMERS AND DERIVATIVES THEREOF,” both of whichare herein incorporated by reference in their entirety for all purposes.

FIELD OF THE INVENTION

The present invention relates to medical electrical leads, and morespecifically to medical electrical leads and lead componentsincorporating polyisobutylene based urethane, urea and urethane/ureacopolymers and their derivatives.

BACKGROUND OF THE INVENTION

Polymeric materials such as silicone rubber, polyurethane, and otherpolymers are used as insulation materials for medical electrical leads.For cardiac rhythm management systems, such leads are typically extendedintravascularly to an implantation location within or on a patient'sheart, and thereafter coupled to a pulse generator or other implantabledevice for sensing cardiac electrical activity, delivering therapeuticstimuli, and the like. The leads are desirably highly flexible toaccommodate natural patient movement, yet also constructed to haveminimized profiles.

During and after implantation, the leads and lead body materials areexposed to various external conditions imposed, for example, by thehuman muscular, skeletal and cardiovascular systems, body fluids, thepulse generator, other leads, and surgical instruments used duringimplantation and explanation procedures. Accordingly, there are ongoingefforts to identify lead body materials that are able to withstand avariety of conditions over a prolonged period of time while maintainingdesirable flexibility characteristics and a minimized profile.

SUMMARY OF THE INVENTION

A first example provides an implantable medical lead comprising anelongated lead body comprising a lumen, at least one conductor disposedwithin the lumen and at least one electrode operatively coupled to theconductor and disposed along the lead body, wherein the lead body has ashore hardness ranging from about 30A to about 75D and comprises apolyisobutylene urethane, urea or urethane/urea copolymer comprisingsoft polymer segments and hard polymer segments. The soft polymersegments comprise a polyisobutylene segment and at least one additionalpolymer segment comprising a residue of a polyether diol, a fluorinatedpolyether diol, a fluoropolymer diol, a polyester diol, a polyacrylatediol, a polymethacrylate diol, a polysiloxane diol, a fluorinatedpolysiloxane diol, or a polycarbonate diol. A weight ratio of softsegments to hard segments in the copolymer ranges from 50:50 to 90:10.

A second example is an implantable medical lead according to example 1,wherein a weight ratio of polyisobutylene to additional polymer rangesfrom about 70:30 to about 90:10.

A third example is an implantable medical lead according to any of theforegoing examples, wherein the soft segments comprise a polyisobutylenesegment and a residue of a polyether diol.

A fourth example is an implantable medical lead according to any of theforegoing examples wherein the soft segments comprise a polyisobutylenesegment and a residue of a polytetramethylene oxide diol

A fifth example is an implantable medical lead according to any of theforegoing examples, wherein a weight ratio of polyisobutylene topolytetramethylene oxide ranges from about 70:30 to about 90:10.

A sixth example is an implantable medical lead according to any of theforegoing examples, wherein the polyisobutylene segment comprises aresidue of an unsaturated polyisobutylene diol.

A seventh example is an implantable medical lead according to any of theforegoing examples wherein the lead body comprises an inner lumen and aninner surface of the lumen comprises the copolymer.

An eighth example is an implantable medical lead according to any of theforegoing examples, wherein the conductor is a coiled conductor having aco-radial configuration and wherein the inner surface is disposed overan outer surface of the coiled conductor.

A ninth example is an implantable medical lead according to any of theforegoing examples, wherein the lead body comprises an inner tubularlayer and an outer tubular layer, wherein at least one of the inner andouter tubular layers comprises a polyisobutylene urethane, urea orurethane/urea copolymer.

A tenth example is an implantable medical lead according to any of theforegoing examples, wherein the lead comprises first and second coiledconductors having a co-axial configuration, wherein the inner tubularlayer is disposed between the first and the second conductors, andwherein the outer tubular layer is disposed over the second coiledconductor.

An eleventh example is an implantable medical lead comprising anelongated lead body comprising a lumen, at least one conductor disposedwithin the lumen and at least one electrode operatively coupled to theconductor and disposed along the lead body, wherein the lead bodycomprises a polyisobutylene urethane, urea or urethane/urea copolymer ineach of a proximal region comprising a first shore hardness, a middleregion comprising a second shore hardness and a distal region comprisinga third shore hardness. The copolymer comprises soft polymer segmentsand hard polymer segments and wherein the soft polymer segments comprisea residue of a polyether diol, a fluorinated polyether diol, afluoropolymer diol, a polyester diol, a polyacrylate diol, apolymethacrylate diol, a polysiloxane diol, a fluorinated polysiloxanediol, or a polycarbonate diol.

A twelve example is an implantable medical lead according to any of theforegoing claims, wherein the distal region comprises a shore hardnessranging from about 30A to about 70A.

A thirteenth example is an implantable medical lead according to any ofthe foregoing claims, wherein the middle region comprises a shorehardness ranging from about 60A to about 85A.

A fourteenth example is an implantable medical lead according to any ofthe foregoing claims, wherein the proximal region comprises a shorehardness ranging from about 85A to about 100A.

A fifteenth example is an implantable medical lead according to any ofthe foregoing claims, wherein soft segment in each region comprises aresidue of a polytetramethylene oxide diol.

A sixteenth example is an implantable medical lead according to any ofthe foregoing claims, wherein a weight ratio of polyisobutylene topolytetramethylene in each region ranges from about 70:30 to about90:10.

A seventeenth example is an implantable medical lead according to any ofthe foregoing claims, wherein a weight ratio of soft segments to hardsegments in the copolymer in each region ranges from 50:50 to 90:10.

An eighteenth example is an implantable medical lead according to any ofthe foregoing claims, wherein the proximal region comprises a firstweight ratio of soft segments to hard segments in the polyisobutyleneurethane, urea or urethane/urea copolymer, the middle region comprises asecond weight ratio of soft segments to hard segments in thepolyisobutylene urethane, urea or urethane/urea copolymer, and thedistal region comprises a third weight ratio of soft segments to hardsegments in the polyisobutylene urethane, urea or urethane/ureacopolymer.

A nineteenth example is an implantable medical lead comprising aflexible, elongated lead body comprising an inner tubular memberincluding at least one longitudinal lumen therethrough; at least oneconductor extending through the at least one lumen of the inner tubularmember, the conductor including an electrode having an exposed surfacerelative to the lead body; and at least one polymeric componentconnected to at least one of the lead body, conductor and electrode, theat least one polymeric component comprising a polyisobutylene urethane,urea or urethane/urea copolymer. The copolymer comprises soft polymersegments and hard polymer segments and the soft polymer segmentscomprise a polyisobutylene segment and at least one additional polymersegment comprising a residue of a polyether diol, a fluorinatedpolyether diol, a fluoropolymer diol, a polyester diol, a polyacrylatediol, a polymethacrylate diol, a polysiloxane diol, a fluorinatedpolysiloxane diol, or a polycarbonate diol.

A twentieth example is an implantable medical lead according to any ofthe foregoing claims, wherein the at least one polymeric componentcomprises a lead terminal, terminal pin, a lead tip, O-ring, seal or aheader.

A twenty-first example is an implantable medical lead according to anyof the foregoing claims, wherein the at least one polymeric componentcomprises a thin film disposed on or adjacent to the exposed surface ofthe electrode.

A twenty-second example is an implantable medical lead according to anyof the foregoing claims, wherein the thin film comprises a plurality ofelectrospun fibers comprising the polyisobutylene urethane, urea orurethane/urea copolymer.

A twenty-third example is an implantable medical lead according to anyof the foregoing claims, wherein the at least one polymeric layercomprises a polymer tube disposed adjacent to the exposed surface of theelectrode.

A twenty-fourth example is a method of manufacturing an implantablemedical lead comprising forming a lead body portion having a shorehardness ranging from about 30A to about 75D from a polymer materialcomprising a polyisobutylene urethane, urea or urethane/urea copolymer,wherein the copolymer comprises soft polymer segments and hard polymersegments in a weight ratio of from 50:50 to 90:10. The soft polymersegments comprise a polyisobutylene segment and at least one additionalpolymer segment comprising a residue of a polyether diol, a fluorinatedpolyether diol, a fluoropolymer diol, a polyester diol, a polyacrylatediol, a polymethacrylate diol, a polysiloxane diol, a fluorinatedpolysiloxane diol, or a polycarbonate diol. The lead body portion isassociated with a conductor and an electrode connected to the conductor.

A twenty-fifth example is an implantable medical lead according to anyof the foregoing examples wherein the lead body portion is formed byextruding the polymer material.

A twenty-sixth example is an implantable medical lead according to anyof the foregoing examples, wherein the polyisobutylene urethane, urea orurethane/urea copolymer comprises an unsaturated polyisobutylenesegment.

A twenty-seventh example is an implantable medical lead according to anyof the foregoing examples, wherein the polyisobutylene urethane, urea orurethane/urea copolymer comprises a polyisobutylene segment formed froma saturated polyisobutylene diol having a number average molecularweight of between about 1000 and 5000.

A twenty-eighth example is an implantable medical lead according to anyof the foregoing examples, wherein the polyisobutylene urethane, urea orurethane/urea copolymer comprises a polytetramethylene oxide segmentformed from a polytetramethylene oxide diol having a number averagemolecular weight of between about 500 and 3000.

A twenty-ninth example is an implantable medical lead according to anyof the foregoing examples, further comprising the step of combining thepolyisobutylene urethane, urea or urethane/urea copolymer with at leastone processing aid, antioxidant or wax to form a mixture.

A thirtieth example is an implantable medical lead according to any ofthe foregoing examples, further comprising the step of extruding thelead body portion from the mixture.

A thirty-first example is an implantable medical lead according to anyof the foregoing examples, wherein forming the lead body portioncomprises forming a proximal region including a first shore hardness, amiddle region comprising a second shore hardness and a distal regioncomprising a third shore hardness, wherein each of the first, second andthird regions comprises the polyisobutylene urethane, urea orurethane/urea copolymer.

A thirty-second example is an implantable medical lead according to anyof the foregoing examples, wherein the proximal region comprises a firstweight ratio of soft segments to hard segments in the polyisobutyleneurethane, urea or urethane/urea copolymer, the middle region comprises asecond weight ratio of soft segments to hard segments in thepolyisobutylene urethane, urea or urethane/urea copolymer, and thedistal region comprises a third weight ratio of soft segments to hardsegments in the polyisobutylene urethane, urea or urethane/ureacopolymer.

A thirty-third example is an implantable medical lead according to anyof the foregoing examples, wherein the forming step compriseselectrospinning the polyisobutylene urethane, urea or urethane/ureacopolymer.

A thirty-fourth example is a method for forming a medical electricallead having coiled electrode including a polymeric layer, the methodcomprising electrospinning multiple fibers comprising a polyisobutyleneurethane, urea or urethane/urea copolymer; and depositing the fibersonto at least a portion of the coiled electrode to form the polymericlayer.

A thirty-fifth example is an implantable medical lead according to anyof the foregoing examples, further comprising the step ofelectrospinning the fibers directly onto the coiled electrode.

A thirty-sixth example is an implantable medical lead according to anyof the foregoing examples, further comprising the step ofelectrospinning the fibers onto a substrate to form a fibrous thin filmand wrapping multiple layers of the fibrous thin film over the coiledelectrode.

A thirty-seventh example is an implantable medical lead according to anyof the foregoing examples, medical electrical lead according to claim534, wherein the proximal region comprises a durometer ranging fromabout 85A to about 70A, the middle region comprises a durometer rangingfrom about 60A to about 85A, and the distal region comprises a durometerranging from about 30A to about 70A.

These and other aspects and embodiments as well as various advantages ofthe present invention will become readily apparent to those of ordinaryskill in the art upon review of the Detailed Description and any Claimsto follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of an implantable cardiac deviceincluding a lead shown implanted in a sectional view of a heart.

FIG. 2 is a perspective view of a medical electrical lead according toanother embodiment of the present invention.

FIGS. 3A-3C are schematic illustrations of polymeric lead components, inaccordance with three embodiments of the invention.

FIG. 4A is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with an embodiment of the invention.

FIGS. 4B and 4C are alternative expanded views of a portion of FIG. 4A.

FIG. 5 is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with yet another embodiment of theinvention.

FIG. 6A is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with another embodiment of the invention.FIG. 6B is a cross section of the medical lead of FIG. 6A, taken alongline B-B.

FIG. 7A is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with another embodiment of the invention.FIG. 7B is a cross section of the medical lead of FIG. 7A, taken alongline B-B.

FIG. 8 is a partial schematic view of a portion of a medical lead inaccordance with an embodiment of the invention.

FIG. 9 is a cross section of the medical lead of FIG. 8, taken alongline B-B.

FIG. 10 is a cross section of the medical lead of FIG. 8, taken alongline B-B, in an alternative embodiment to FIG. 9.

FIG. 11 is an end cross-sectional view of a portion of a medicalelectrical lead provided in accordance with another embodiment of thepresent invention.

FIGS. 12A and 12B are end cross-section views of a portion of a lead,body provided in accordance with yet other embodiments of the presentinvention.

FIG. 13 is a longitudinal cross-sectional view of a portion of a leadbody including a coiled electrode according to another embodiment of thepresent invention.

FIG. 14 is a plot of weight loss versus time for representativepolyisobutylene urethane copolymer samples containing PTMO.

FIG. 15 is a plot of weight loss at 12 weeks versus PTMO content forrepresentative polyisobutylene urethane copolymer samples.

FIG. 16 is a representative FTIR spectrum of a polyisobutylene urethanecopolymer containing PTMO.

FIG. 17 is a representative FTIR spectrum of a polyisobutylene urethanecopolymer including a saturated PIB diol.

FIGS. 18 and 19 are FTIR spectra of representative PELLATHANE™ samples.

FIGS. 20 and 21 are GPC refractive index traces of representativePELLATHANE™ samples.

FIG. 22 is a representative GPC refractive index trace for arepresentative polyisobutylene urethane copolymer containing a saturatedPIB diol.

FIG. 23 is a plot of tensile strength versus time for variousrepresentative samples.

FIG. 24 shows scanning electron microscope (SEM) photos taken at 300×magnification of representative PELLETHANE™ samples.

FIG. 25 shows scanning electron microscope (SEM) photos taken at 300×magnification of representative polyisobutylene urethane copolymersamples.

FIGS. 26 and 27 are bar graphs showing the loss in mass (degradation) at3 weeks and at 6 weeks for various test samples.

FIGS. 28-29 show FTIR spectra of two representative PELLATHANE™ samplessubjected to accelerated degradation testing taken at 0 weeks and 3weeks.

FIG. 30 shows FTIR spectra of an ELASTEON sample subjected toaccelerated degradation testing taken at 0 weeks and 3 weeks.

FIG. 31 shows FTIR spectra of a representative PI-PU sample subjected toaccelerated degradation testing at 0 weeks and 3 weeks.

FIG. 32 shows comparative scanning electron microscope (SEM) photos ofvarious test samples subjected to accelerated degradation testing takenat 0 weeks and 3 weeks.

DETAILED DESCRIPTION OF THE INVENTION

A more complete understanding of the present invention is available byreference to the following detailed description of numerous aspects andembodiments of the invention. The detailed description of the inventionwhich follows is intended to illustrate but not limit the invention.

In accordance with various aspects of the invention, implantable andinsertable medical devices are provided, which include one or morepolymeric regions containing one or more polyisobutylene urethane, ureaor urethane/urea copolymers (also referred to herein collectively as“polyisobutylene urethane copolymers”). As used herein, a “polymericregion” is a region (e.g., an entire device, an insulative layer, adevice component, a device coating layer, etc.) that contains polymers,for example, from 50 wt % or less to 75 wt % to 90 wt % to 95 wt % to97.5 wt % to 99 wt % or more polymers.

Medical electrical devices of the present invention typically include(a) an electronic signal generating component and (b) one or more leads.The electronic signal generating component commonly contains a source ofelectrical power (e.g., a sealed battery) and an electronic circuitrypackage, which produces electrical signals that are sent into the body(e.g., the heart, nervous system, etc.). Leads comprise at least oneflexible elongated conductive member (e.g., a wire, cable, etc.), whichis insulated along at least a portion of its length, generally by anelongated polymeric component often referred to as a lead body. Theconductive member is adapted to place the electronic signal generatingcomponent of the device in electrical communication with one or moreelectrodes, which provide for electrical connection with the body. Leadsare thus able to conduct electrical signals to the body from theelectronic signal generating component. Leads may also relay signalsfrom the body to the electronic signal generating component.

Examples of medical electrical devices of the present invention include,for example, implantable electrical stimulation systems includingneurostimulation systems such as spinal cord stimulation (SCS) systems,deep brain stimulation (DBS) systems, peripheral nerve stimulation (PNS)systems, gastric nerve stimulation systems, cochlear implant systems,and retinal implant systems, among others, and cardiac systems includingimplantable cardiac rhythm management (CRM) systems, implantablecardioverter-defibrillators (ICD's), and cardiac resynchronization anddefibrillation (CRDT) devices, among others.

FIG. 1 is a schematic illustration of a lead system 100 for deliveringand/or receiving electrical pulses or signals to stimulate, shock,and/or sense the heart 102. The system 100 includes a pulse generator105 and a lead 110. The pulse generator 105 includes a source of poweras well as an electronic circuitry portion. The pulse generator 105 is abattery-powered device which generates a series of timed electricaldischarges or pulses. The pulse generator 105 is generally implantedinto a subcutaneous pocket made in the wall of the chest. Alternatively,the pulse generator 105 may be placed in a subcutaneous pocket made inthe abdomen, or in another location. It should be noted that while thelead 110 is illustrated for use with a heart, the lead 110 is suitablefor other forms of electrical stimulation/sensing as well. For example,the lead 110 can be used for neurostimulation. Examples ofneurostimulation leads and instruments for their implantation arereported in, e.g., U.S. Pat. No. 7,292,890 to Whitehurst et al., U.S.Pat. No. 6,600,956 to Maschino et al., and U.S. Pat. No. 6,093,197 toBakula et al, which are hereby incorporated by reference.

The lead 110 extends from a proximal end 112, where it is coupled withthe pulse generator 105 to a distal end 114, which is coupled with aportion of a heart 102, when implanted or otherwise coupled therewith.An outer insulating lead body extends generally from the proximal end112 to the distal end 114 of the lead 110. Also disposed along a portionof the lead 110, for example near the distal end 114 of the lead 110, isat least one electrode 116 which electrically couples the lead 110 withthe heart 102. At least one electrical conductor (not shown) is disposedwithin the lead body and extends generally from the proximal end 112 tothe distal end 114 of the lead 110. The at least one electricalconductor electrically couples the electrode 116 with the proximal end112 of the lead 110. The electrical conductor carries electrical currentand pulses between the pulse generator 105 and the electrode 116, and toand from the heart 102. In one option, the at least one electricalconductor is a coiled conductor. In another option, the at least oneelectrical conductor includes one or more cables. Typical lengths forsuch leads vary from about 35 cm to 40 cm to 50 cm to 60 cm to 70 cm to80 cm to 90 cm to 100 cm to 110 cm to 120 cm, among other values.Typical lead diameters vary from 4 to 5 to 6 to 7 to 8 to 9 French,among other values.

As noted above, portions of the medical electrical devices of thepresent invention are formed from or contain polyisobutylene urethanecopolymers as further described herein. These polyisobutylene urethanecopolymers may be used to form a variety of polymeric components formedical electrical devices (e.g., pacemakers, defibrillators, heartfailure devices, neurostimulation devices, etc.) including portions ofthe lead body through which at least one conductor extends, such assingle-lumen and multi-lumen extrusions and inner and outer tubular(tube-shaped) insulation layers, as well as lead tip materials, headers,and various other lead components (e.g., seal O-rings, etc.).

The polyisobutylene urethane copolymers described herein may also beused as encapsulation/insulation materials for electronic signalgenerating/sensing components, examples of which include implantablepulse generators, implantable cardioverter-defibrillators (ICDs) andimplantable cardiac resynchronization therapy (CRT) devices. Suchelectronic signal generating/sensing components may be used, forexample, in conjunction with right ventricular lead systems, rightatrial lead systems, and left atrial/ventricular lead systems and may beused to treat, for example, bradycardia, tachycardia (e.g., ventriculartachycardia) or cardiac dyssynchrony in a vertebrate subject (includinghumans, pets and livestock). As previously noted, the present inventionis also applicable to leads and electronic signal generating/sensingcomponents for neurostimulation systems such as spinal cord stimulation(SCS) systems, deep brain stimulation (DBS) systems, peripheral nervestimulation (PNS) systems, gastric nerve stimulation systems, cochlearimplant systems, retinal implant systems, and pain management systems,among others.

As is well known, “polymers” are molecules containing multiple copies(e.g., from 5 to 10 to 25 to 50 to 100 to 250 to 500 to 1000 or morecopies) of one or more constitutional units, commonly referred to asmonomers. As used herein, the term “monomers” may refer to free monomersand to those that have been incorporated into polymers, with thedistinction being clear from the context in which the term is used.

Polymers may take on a number of configurations including linear, cyclicand branched configurations, among others. Branched configurationsinclude star-shaped configurations (e.g., configurations in which threeor more chains emanate from a single branch point), comb configurations(e.g., configurations having a main chain and a plurality of sidechains, also referred to as “graft” configurations), dendriticconfigurations (e.g., arborescent and hyperbranched polymers), and soforth.

As used herein, “homopolymers” are polymers that contain multiple copiesof a single constitutional unit (i.e., a monomer). “Copolymers” arepolymers that contain multiple copies of at least two dissimilarconstitutional units.

Polyurethanes are a family of copolymers that are synthesized frompolyfunctional isocyanates (e.g., diisocyanates, including bothaliphatic and aromatic diisocyanates) and polyols (e.g., macroglycols).Commonly employed macroglycols include polyester diols, polyether diolsand polycarbonate diols that form polymeric segments of thepolyurethane. Typically, aliphatic or aromatic diols or diamines arealso employed as chain extenders, for example, to impart improvedphysical properties to the polyurethane. Where diamines are employed aschain extenders, urea linkages are formed and the resulting polymers maybe referred to as polyurethane/polyureas.

Polyureas are a family of copolymers that are synthesized frompolyfunctional isocyanates and polyamines, for example, diamines such aspolyester diamines, polyether diamines, polysiloxane diamines,polyhydrocarbon diamines and polycarbonate diamines. As withpolyurethanes, aliphatic or aromatic diols or diamines may be employedas chain extenders.

According to certain aspects of the invention, the polyisobutyleneurethane copolymer includes (a) one or more polyisobutylene segments,(b) one or more additional polymeric segments (other thanpolyisobutylene segments), (c) one or more segments that includes one ormore diisocyanate residues, and optionally (d) one or more chainextenders. Examples of such copolymers and methods for their synthesisare generally described in WO 2008/060333, WO 2008/066914 and U.S.application Ser. No. 12/492,483 filed on Jun. 26, 2009 entitledPOLYISOBUTYLENE URETHANE, UREA AND URETHANE/UREA COPOLYMERS AND MEDICALDEVICES CONTAINING THE SAME, all of which are incorporated herein byreference in their entirety.

As used herein, a “polymeric segment” or “segment” is a portion of apolymer. Segments can be unbranched or branched. Segments can contain asingle type of constitutional unit (also referred to herein as“homopolymeric segments”) or multiple types of constitutional units(also referred to herein as “copolymeric segments”) which may bepresent, for example, in a random, statistical, gradient, or periodic(e.g., alternating) distribution.

The polyisobutylene segments of the polyisobutylene urethane copolymersare generally considered to constitute soft segments, while the segmentscontaining the diisocyanate residues are generally considered toconstitute hard segments. The additional polymeric segments may includesoft or hard polymeric segments. As used herein, soft and hard segmentsare relative terms to describe the properties of polymer materialscontaining such segments. Without limiting the foregoing, a soft segmentmay display a Tg that is below body temperature, more typically from 35°C. to 20° C. to 0° C. to −25° C. to −50° C. or below. A hard segment maydisplay a Tg that is above body temperature, more typically from 40° C.to 50° C. to 75° C. to 100° C. or above. Tg can be measured bydifferential scanning calorimetry (DSC), dynamic mechanical analysis(DMA) and thermomechanical analysis (TMA).

Suitable soft segments include linear, branched or cyclic polyalkyl,polyalkene and polyalkenyl segments, polyether segments, fluoropolymersegments including fluorinated polyether segments, polyester segments,poly(acrylate) segments, poly(methacrylate) segments, polysiloxanesegments and polycarbonate segments.

Examples of suitable polyether segments include linear, branched andcyclic homopoly(alkylene oxide) and copoly(alkylene oxide) segments,including homopolymeric and copolymeric segments formed from one ormore, among others, methylene oxide, dimethylene oxide (ethylene oxide),trimethylene oxide, propylene oxide, tetramethylene oxide,pentamethylene oxide, hexamethylene oxide, octamethylene oxide anddecamethylene oxide.

Examples of suitable fluoropolymer segments include perfluoroacrylatesegments and fluorinated polyether segments, for example, linear,branched and cyclic homopoly(fluorinated alkylene oxide) andcopoly(fluorinated alkylene oxide) segments, including homopolymeric andcopolymeric segments formed from one or more of, among others,perfluoromethylene oxide, perfluorodimethylene oxide (perfluoroethyleneoxide), perfluorotrimethylene oxide and perfluoropropylene oxide.

Examples of suitable polyester segments include linear, branched andcyclic homopolymeric and copolymeric segments formed from one or moreof, among others, alkyleneadipates including ethyleneadipate,propyleneadipate, tetramethyleneadipate, and hexamethyleneadipate.

Examples of suitable poly(acrylate) segments include linear, branchedand cyclic homopoly(acrylate) and copoly(acrylate) segments, includinghomopolymeric and copolymeric segments formed from one or more of, amongothers, alkyl acrylates such as methyl acrylate, ethyl acrylate, propylacrylate, isopropyl acrylate, butyl acrylate, sec-butyl acrylate,isobutyl acrylate, 2-ethylhexyl acrylate and dodecyl acrylate.

Examples of suitable poly(methacrylate) segments include linear,branched and cyclic homopoly(methacrylate) and copoly(methacrylate)segments, including homopolymeric and copolymeric segments formed fromone or more of, among others, alkyl methacrylates such as hexylmethacrylate, 2-ethylhexyl methacrylate, octyl methacrylate, dodecylmethacrylate and octadecyl methacrylate.

Examples of suitable polysiloxane segments include linear, branched andcyclic homopolysiloxane and copolysiloxane segments, includinghomopolymeric and copolymeric segments formed from one or more of, amongothers, dimethyl siloxane, diethyl siloxane, and methylethyl siloxane.

Examples of suitable polycarbonate segments include those comprising oneor more types of carbonate units,

where R may be selected from linear, branched and cyclic alkyl groups.Specific examples include homopolymeric and copolymeric segments formedfrom one or more of, among others, ethylene carbonate, propylenecarbonate, and hexamethylene carbonate.

Examples of hard polymeric segments include various poly(vinyl aromatic)segments, poly(alkyl acrylate) and poly(alkyl methacrylate) segments.

Examples of suitable poly(vinyl aromatic) segments include linear,branched and cyclic homopoly(vinyl aromatic) and copoly(vinyl aromatic)segments, including homopolymeric and copolymeric segments formed fromone or more vinyl aromatic monomers including, among others, styrene,2-vinyl naphthalene, alpha-methyl styrene, p-methoxystyrene,p-acetoxystyrene, 2-methylstyrene, 3-methylstyrene and 4-methylstyrene.

Examples of suitable poly(alkyl acrylate) segments include linear,branched and cyclic homopoly(alkyl acrylate) and copoly(alkyl acrylate)segments, including homopolymeric and copolymeric segments formed fromone or more acrylate monomers including, among others, tert-butylacrylate, hexyl acrylate and isobornyl acrylate.

Examples of suitable poly(alkyl methacrylate) segments include linear,branched and cyclic homopoly(alkyl methacrylate) and copoly(alkylmethacrylate) segments, including homopolymeric and copolymeric segmentsformed from one or more alkyl methacrylate monomers including, amongothers, methyl methacrylate, ethyl methacrylate, isopropyl methacrylate,isobutyl methacrylate, t-butyl methacrylate, and cyclohexylmethacrylate.

Particularly suitable polyisobutylene urethane copolymers include (a) apolyisobutylene soft segment, (b) a polyether soft segment, (c) a hardsegment containing diisocyanate residues, (d) optional chain extendersas further described below and/or (e) optional end capping materials asfurther described below.

The weight ratio of soft segments to hard segments in thepolyisobutylene urethane copolymers of the present invention can bevaried to achieve a wide range of physical and mechanical properties,including Shore hardness, and to achieve an array of desirablefunctional performance. For example, the weight ratio of soft segmentsto hard segments in the polymer can be varied from 99:1 to 95:5 to 90:10to 75:25 to 50:50 to 25:75 to 10:90 to 5:95 to 1:99, more particularlyfrom 95:5 to 90:10 to 80:20 to 70:30 to 65:35 to 60:40 to 50:50, andeven more particularly, from about 80:20 to about 50:50.

The shore hardness of the polyisobutylene urethane copolymers ofembodiments of the present invention can be varied by controlling theweight ratio of soft segments to hard segments. Suitable short hardnessranges include for example, from 45A, more particularly from 50A to52.5A to 55A to 57.5A to 60A to 62.5A to 65A to 67.5A to 70A to 72.5A to75A to 77.5A to 80A to 82.5A to 85A to 87.5A to 90A to 92.5A to 95A to97.5A to 100A. In one embodiment, a polyisobutylene urethane copolymerwith a soft segment to hard segment weight ratio of 80:20 results in aShore Hardness of about 60-71A, a polyisobutylene urethane copolymerhaving a soft segment to hard segment weight ratio of 65:35 results in aShore hardness of 80-83A, a polyisobutylene urethane copolymer having asoft segment to hard segment weight ratio of 60:40 result in a Shorehardness 95-99A, and a polyisobutylene urethane copolymer having a softsegment to hard segment weight ratio of 50:50 result in a Shorehardness >100A. Higher hardness materials (e.g., 55 D and above up to 75D) can also be prepared by increasing the ratio of hard to softsegments. Such harder materials may be particularly suitable for use inthe PG header device, tip and pin areas of leads and headers ofneuromodulation cans.

The polyisobutylene and additional polymeric segments can vary widely inmolecular weight, but typically are composed of between 2 and 100 repeatunits (monomer units), among other values, and can be incorporated intothe polyisobutylene polyurethane copolymers of the invention in the formof polyol (e.g., diols, triols, etc.) or polyamine (e.g., diamines,triamines, etc.) starting materials. Although the discussion to followis generally based on the use of polyols, analogous methods may beperformed and analogous compositions may be created using polyamines andpolyol/polyamine combinations.

Suitable polyisobutylene polyol starting materials include linearpolyisobutylene diols and branched (three-arm) polyisobutylene triols.More specific examples include linear polyisobutylenediols with aterminal —OH functional group at each end. Further examples ofpolyisobutylene polyols include poly(styrene-co-isobutylene) diols andpoly(styrene-b-isobutylene-b-styrene) diols which may be formed, forexample, using methods analogous to those described in See, e.g., J. P.Kennedy et al., “Designed Polymers by Carbocationic MacromolecularEngineering: Theory and Practice,” Hanser Publishers 1991, pp. 191-193,Joseph P. Kennedy, Journal of Elastomers and Plastics 1985 17: 82-88,and the references cited therein. The polyisobutylene diol startingmaterials can be formed from a variety of initiators as known in theart. In one embodiment, the polyisobutylene diol starting material is asaturated polyisobutylene diol that is devoid of C═C bonds.

Examples of suitable polyether polyol starting materials includepolytetramethylene oxide diols and polyhexamethylene diols, which areavailable from various sources including Sigma-Aldrich Co., Saint Louis,Mo., USA and E.I. duPont de Nemours and Co., Wilmington, Del., USA.Examples of polysiloxane polyol starting materials includepolydimethylsiloxane diols, available from various sources including DowCorning Corp., Midland Mich., USA, Chisso Corp., Tokyo, Japan. Examplesof suitable polycarbonate polyol starting materials includepolyhexamethylene carbonate diols such as those available fromSigma-Aldrich Co. Examples of polyfluoroalkylene oxide diol startingmaterials include ZDOLTX, Ausimont, Bussi, Italy, acopolyperfluoroalkylene oxide diol containing a random distribution of—CF₂CF₂O— and —CF₂O— units, end-capped by ethoxylated units, i.e.,H(OCH₂CH₂)_(n)OCH₂CF₂O(CF₂CF₂O)_(p)(CF₂O)_(q)CF₂CH₂O(CH₂CH₂O)_(n)H,where n, p and q are integers. Suitable polystyrene diol startingmaterials (α,ω-dihydroxy-terminated polystyrene) of varying molecularweight are available from Polymer Source, Inc., Montreal, Canada.Polystyrene diols and three-arm triols may be formed, for example, usingprocedures analogous to those described in M. Weiβmüller et al.,“Preparation and end-linking of hydroxyl-terminated polystyrene starmacromolecules,” Macromolecular Chemistry and Physics 200(3), 1999,541-551.

In some embodiments, polyols (e.g., diols, triols, etc.) are synthesizedas block copolymer polyols. Examples of such block copolymer polyolsinclude poly(tetramethylene oxide-b-isobutylene) diol,poly(tetramethylene oxide-b-isobutylene-b-tetramethylene oxide) diol,poly(dimethyl siloxane-b-isobutylene) diol, poly(dimethylsiloxane-b-isobutylene-b-dimethyl siloxane) diol, poly(hexamethylenecarbonate-b-isobutylene) diol, poly(hexamethylenecarbonate-b-isobutylene-b-hexamethylene carbonate) diol, poly(methylmethacrylate-b-isobutylene) diol, poly(methylmethacrylate-b-isobutylene-b-methyl methacrylate) diol,poly(styrene-b-isobutylene) diol andpoly(styrene-b-isobutylene-b-styrene) diol (SIBS diol).

Diisocyanates for use in forming the urethane copolymers of theinvention include aromatic and non-aromatic (e.g., aliphatic)diisocyanates. Aromatic diisocyanates may be selected from suitablemembers of the following, among others: 4,4′-methylenediphenyldiisocyanate (MDI), 2,4- and/or 2,6-toluene diisocyanate (TDI),1,5-naphthalene diisocyanate (NDI), para-phenylene diisocyanate,3,3′-tolidene-4,4′-diisocyanate and3,3′-dimethyl-diphenylmethane-4,4′-diisocyanate. Non-aromaticdiisocyanates may be selected from suitable members of the following,among others: 1,6-hexamethylene diisocyanate (HDI),4,4′-dicyclohexylmethane diisocyanate,3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate (isophoronediisocyanate or IPDI), cyclohexyl diisocyanate, and2,2,4-trimethyl-1,6-hexamethylene diisocyanate (TMDI).

In a particular embodiment, a polyether diol such as polytetramethyleneoxide diol (PTMO diol), polyhexametheylene oxide diol (PHMO diol),polyoctamethylene oxide diol or polydecamethylene oxide diol is combinedwith the polyisobutylene diol and diisocyanate to form a polyisobutylenepolyurethane copolymer with generally uniform distribution of thepolyurethane hard segments, polyisobutylene segments and polyethersegments to achieve favorable micro-phase separation in the polymer. Thepolyether segments may also improve key mechanical properties such asShore hardness, tensile strength, tensile modulus, flexural modulus,elongation, tear strength, flex fatigue, tensile creep, and abrasionperformance, among others.

The polyisobutylene urethane copolymers in accordance with the inventionmay further include one or more optional chain extender residues and/orend groups. Chain extenders can increase the hard segment length (or,stated another way, can increase the ratio of hard segment material tosoft segment material in the urethane, urea or urethane/urea polymer),which can in turn result in a polymer with higher modulus, lowerelongation at break and increased strength. For instance the molar ratioof soft segment to chain extender to diisocyanate (SS:CE:DI) can range,for example, from 1:9:10 to 2:8:10 to 3:7:10 to 4:6:10 to 5:5:10 to6:4:10 to 7:3:10 to 8:2:10 to 9:1:10.

Chain extenders are typically formed from aliphatic or aromatic diols(in which case a urethane bond is formed upon reaction with anisocyanate group) or aliphatic or aromatic diamines (in which case aurea bond is formed upon reaction with an isocyanate group). Chainextenders may be selected from suitable members of the following, amongothers: alpha,omega-alkane diols such as ethylene glycol (1,2-ethanediol), 1,4-butanediol, 1,6-hexanediol, alpha,omega-alkane diamines suchas ethylene diamine, dibutylamine (1,4-butane diamine) and1,6-hexanediamine, or 4,4′-methylene bis(2-chloroaniline). Chainextenders may be also selected from suitable members of, among others,short chain diol polymers (e.g., alpha,omega-dihydroxy-terminatedpolymers having a molecular weight less than or equal to 1000) based onhard and soft polymeric segments (more typically soft polymericsegments) such as those described above, including short chainpolyisobutylene diols, short chain polyether polyols such aspolytetramethylene oxide diols, short chain polysiloxane diols such aspolydimethylsiloxane diols, short chain polycarbonate diols such aspolyhexamethylene carbonate diols, short chain poly(fluorinated ether)diols, short chain polyester diols, short chain polyacrylate diols,short chain polymethacrylate diols, and short chain poly(vinyl aromatic)diols.

In certain embodiments, the biostability and/or biocompatibility of thepolyisobutylene urethane copolymers in accordance with the invention maybe improved by end-capping the copolymers with short aliphatic chains(e.g., [—CH₂]_(n)—CH₃ groups, [—CH₂]_(n)—C(CH₃)₃ groups, [—CH₂]_(n)—CF₃groups, [—CH₂]_(n)—C(CF₃)₃ groups, [—CH₂]_(n)—CH₂OH groups,[—CH₂]_(n)—C(OH)₃ groups and [—CH₂]_(n)—C₆H₅ groups, etc., where n mayrange, for example, from 1 to 2 to 5 to 10 to 15 to 20, among othersvalues) that can migrate to the polymer surface and self assembleirrespective of synthetic process to elicit desirable immunogenicresponse when implanted in vivo. Alternatively, a block copolymer orblock terpolymer with short aliphatic chains (e.g.,[—CH₂]_(n)-b-[—CH₂O]_(n)—CH₃ groups,[—CH₂]_(n)-b-[—CH₂O]_(n)—CH₂CH₂C(CH₃)₃ groups,[—CH₂]_(n)-b-[—CH₂O]_(n)—CH₂CH₂CF₃ groups,[—CH₂]_(n)-b-[CH₂O]_(n)—CH₂CH₂C(CF₃)₃ groups,[—CH₃]_(n)-b-[CH₂O]_(n)—CH₂CH₂OH groups, [—CH₂]_(n)-b-[—CH₂O]_(n)—C(OH)₃groups, [—CH₂]_(n)-b-[—CH₂O]_(n)—CH₂CH₂—C₆H₅ groups, etc., where n mayrange, for example, from 1 to 2 to 5 to 10 to 15 to 20, among othersvalues) that can migrate to the surface and self assemble can be blendedwith the copolymer toward the end of synthesis. These end-cappingsegments may also help to improve the thermal processing of the polymerby acting as processing aids or lubricants. Processing aids,antioxidants, waxes and the like may also be separately added to aid inthermal processing.

Various techniques may be employed to synthesize the polyisobutyleneurethane copolymers from the diol and diisocyanate starting materials.The reaction may be conducted, for example, in organic solvents or usingsupercritical CO₂ as a solvent. Ionomers can be used for polymerprecipitation.

In certain other embodiments, a one step method may be employed in whicha first macrodiol (M1) (e.g., a polymeric diol such as an unsaturated ora saturated polyisobutylene diol,), a second macrodiol (M2) (e.g., apolyether diol) and a diisocyante (DI) (e.g., MDI, TDI, etc.) arereacted in a single step. Molar ratio of diisocyanate relative to thefirst and second diols is 1:1. For example, the ratio DI:M1:M2 may equal2:1:1, may equal 2:1.5:0.5, may equal 2:0.5:1.5, among many otherpossibilities. Where a ratio of DI:M1:M2 equal to 2:1:1 is employed, apolyurethane having the following structure may be formed-[DI-M1-DI-M2-]_(n) although the chains are unlikely to be perfectlyalternating as shown. In some embodiments, a chain extender is added tothe reaction mixture, such that the molar ratio of diisocyanate relativeto the first and second macrodiols and chain extender is 1:1. Forexample, the ratio DI:M1:M2:CE may equal 4:1:1:2, may equal2:0.67:0.33:1, may equal 2:0.33:0.67:1, or may equal 5:1:1:3, among manyother possibilities. Where a ratio of DI:M1:M2:CE equal to 4:1:1:2 isemployed, a polyurethane having the following structure may be formed-[DI-M1-DI-CE-DI-M2-DI-CE-]_(n), although the chains are unlikely to beperfectly alternating as shown.

In some embodiments, a two-step method is employed in which first andsecond macrodiols and diisocyante are reacted in a ratio of DI:M1:M2 of≧2:1:1 in a first step to form isocyanate capped first and secondmacrodiols, for example DI-M1-DI and DI-M2-DI. In a second step, a chainextender is added which reacts with the isocyanate end caps of themacrodiols. In some embodiments, the number of moles of hydroxyl oramine groups of the chain extender may exceed the number of moles ofisocyanate end caps for the macrodiols, in which case additionaldiisocyante may be added in the second step as needed to maintain asuitable overall stoichiometry. As above, the molar ratio ofdiisocyanate relative to the total of the first macrodiol, secondmacrodiol, and chain extender is typically 1:1, for example, DI:M1:M2:CEmay equal 4:1:1:2, which may in theory yield an idealized polyurethanehaving the following repeat structure -[DI-M1-DI-CE-DI-M2-DI-CE-]_(n),although the chains are unlikely to be perfectly alternating as shown.In other examples, the DI:M1:M2:CE ratio may equal 4:1.5:0.5:2 or mayequal 5:1:1:3, among many other possibilities.

In some embodiments, three, four or more steps may be employed in whicha first macrodiol and diisocyante are reacted in a first step to formisocyanate capped first macrodiol, typically in a DI:M1 ratio of ≧2:1such that isocyanate end caps are formed at each end of the firstmacrodiol (although other ratios are possible including a DI:M1 ratio of1:1, which would yield an average of one isocyanate end caps permacrodiol). This step is followed by second step in which the secondmacrodiol is added such that it reacts with one or both isocyanate endcaps of the isocyanate capped first macrodiol. Depending on the relativeratios of DI, M1 and M2, this step may be used to create structures(among other statistical possibilities) such as M2-DI-M1-DI-M2 (for aDI:M1:M2 ratio of 2:1:2), M2-DI-M1-DI (for a DI:M1:M2 ratio of 2:1:1),or M1-DI-M2 (for a DI:M1:M2 ratio of 1:1:1).

In certain embodiments, a mixed macrodiol prepolymer, such as one ofthose in the prior paragraph, among others (e.g., M2-DI-M1-DI-M2,M1-DI-M2-DI-M1, DI-M1-DI-M2, etc.) is reacted simultaneously with a diolor diamine chain extender and a diisocyanate, as needed to maintainstoichiometry. For example, the chain extension process may be used tocreate idealized structures along the following lines, among others:-[DI-M2-DI-M1-DI-M2-DI-CE-]_(n) or -[DI-M1-DI-M2-DI-CE-]_(n), althoughit is again noted that the chains are not likely to be perfectlyalternating as shown.

In certain other embodiments, a mixed macrodiol prepolymer is reactedwith sufficient diisocyanate to form isocyanate end caps for the mixedmacrodiol prepolymer (e.g., yielding DI-M2-DI-M1-DI-M2-DI,DI-M1-DI-M2-DI-M1-DI or DI-M1-DI-M2-DI, among other possibilities). Thisisocyanate-end-capped mixed macrodiol can then be reacted with a diol ordiamine chain extender (and a diisocyanate, as needed to maintainstoichiometry). For example, the isocyanate-end-capped mixed macrodiolcan be reacted with an equimolar amount of a chain extender to yieldidealized structures of the following formulae, among others:-[DI-M2-DI-M1-DI-M2-DI-CE-]_(n), -[DI-M1-DI-M2-DI-M1-DI-CE-]_(n), or-[DI-M1-DI-M2-DI-CE-]_(n).

As noted above, chain extenders can be employed to increase the ratio ofhard segment material to soft segment material in the urethane, urea orurethane/urea polymers described herein, which can in turn result in apolymer with higher modulus, lower elongation at break and increasedstrength. For instance the molar ratio of soft segment to chain extenderto diisocyanate (SS:CE:DI) can range, for example, from 1:9:10 to 2:8:10to 3:7:10 to 4:6:10 to 5:5:10 to 6:4:10 to 7:3:10 to 8:2:10 to 9:1:10 to10:0:10, among other values.

In a particular embodiment, the soft, segment of the polyisobutyleneurethane copolymer is formed from a first soft macrodiol or macrodiamine(M1) and second soft macrodiol or macrodiamine (M2) in a molar ratio ofM1 to M2 (M1:M2) from 99:1 to 95:5 to 90:10 to 75:25 to 66:33 to 50:50to 25:75 to 10:90 to 5:95 to 1:99, more particularly, from 90:10 to85:15 to 80:20 to 75:25 to 70:30 and most particularly from about 75:25to about 50:50.

Exemplary number average molecular weights for M1 and M2 may range from100 to 10000, more preferably 200 to 5000, most preferably 750 to 2500.Exemplary materials for M1 include polyisobutylene diols, whereaspreferred materials for M2 include polyether diols such aspolytetramethylene oxide (PTMO) diol and polyhexamethylene oxide (PHMO)diol. In one embodiment, M1 is polyisobutylene diol having a numberaverage molecular weight between about 1000 and 5000 and M2 is PTMOhaving a number average molecular weight of about 900 and 1200.

The molar ratio and number average molecular weight of the diol startingmaterials may be used to calculate the weight ratio of first to secondsoft segments in the polyisobutylene urethane copolymer. For example, if48.00 g polyisobutylene diol having a number average molecular weight of1000 is reacted with 32.00 g PTMO having a number average molecularweight of 1000, the weight ratio polyisobutylene segment to PTMO segmentwould be 60:40. In embodiments in which the soft segments includepolyisobutylene and polytetramethylene oxide, the resulting weight ratioranges from 15:1 to 13:1 to 12:1 to 7.5:1 to 4.5:1 to 3:1 to 2:1 to 3:2to 1:1 to 1:2 to 2:3, more particularly, from about 99:1 to 95:5 to90:10 to 80:20 to 70:30.

In another embodiment, the ratio of PIB diol to polytetramethylene oxidediol included in the reaction mixture results in a polyisobutyleneurethane copolymer having soft segments comprising no more than about 30wt % polytetramethylene oxide, particularly between about 10 wt % and 30wt % polytetramethylene oxide, more particularly between about 5 wt %and about 20 wt % polytetramethylene oxide and even more particularlybetween about 10 wt % and about 20 wt % polytetramethylene oxide basedon the total weight of soft segment. The balance of the soft segmentweight may comprise polyisobutylene.

In a further embodiment, the ratio of PIB diol to polyhexamethyleneoxide diol included in the reaction mixture results in a polyisobutyleneurethane copolymer having soft segments comprising no more than about 30wt % polyhexamethylene oxide, particularly between about 10 wt % and 30wt % polyhexamethylene oxide, more particularly between about 15 wt %and 25 wt % polyhexamethylene oxide and even more particularly betweenabout 20 wt % and 25 wt % polyhexamethylene oxide based on the totalweight of soft segment. The balance of the soft segment weight maycomprise polyisobutylene.

Polyisobutylene urethane copolymers containing PTMO of no more thanabout 30% show minimal decrease in both weight and tensile strength andexhibit a continuous surface morphology when subjected to accelerateddegradation testing indicating favorable biostability of thesematerials. Additionally, when the amount of polyether diol (e.g. PTMO)is increased, the degradation also increases, suggesting that a low PTMOcontent promotes biostability.

In yet another exemplary embodiment, the ratio of PIB diol to polyetherdiol (e.g., polytetramethylene oxide diol or polyhexamethylene diol) topolydimethylsiloxane diol included in the reaction mixture results in apolyisobutylene urethane, urea or urethane/urea copolymer having aweight ratio of polyisobutylene to polyether to polydimethylsiloxaneranging from about 60:20:20 to about 80:15:5.

FIG. 2 illustrates a medical electrical lead including an elongated,insulative lead body 110 extending from a proximal end 112 to a distalend 114. According to various embodiments of the present invention, atleast a portion of the lead body is manufactured from a polyisobutyleneurethane copolymer as described above. In some embodiments, thepolyisobutylene urethane copolymer can be extruded or molded into aportion or portions of the lead body. In other embodiments, thepolyisobutylene urethane copolymer can be applied as a coating directlyto the electrical conductors via a variety of techniques including, butnot limited to spray coating, solution coating (dip coating),sputtering, plasma deposition and chemical vapor deposition, amongothers, to form at least a portion of the lead body. In still otherembodiments, the polyisobutylene urethane copolymer can be molded overone or more portions of an existing lead body construction.

In embodiments in which the lead body 110 comprises the polyisobutyleneurethane copolymer, the lead body may have a Shore hardness from about30 A to about 75D and, more particularly, from about 30A to about 55D,even more particularly from about 50A to about 100A. The Shore Hardnessmay remain constant or vary along the length of the lead.

According to another embodiment, the lead body 110 has a Shore hardnessthat varies along its length. The Shore hardness of the lead body can bevaried by utilizing different polyisobutylene urethane copolymerformulations to construct different portions of the lead body, byvarying the composition of a selected polyisobutylene urethane copolymeralong the length of the lead body during the manufacturing processand/or by blending different polyisobutylene urethane copolymers duringmanufacturing to achieve a desired Shore hardness in a selected portionof the lead body.

The lead body 110 shown in FIG. 2 includes multiple discrete regions,the approximate boundaries of which are illustrated by dashed lines.These regions include a proximal region 40, a middle region 42, a distalregion 44 and a lead tip region 46. The proximal region 40 generallyrepresents portions of the lead body 119 that reside in vessels somewhatdistant from the heart. The middle region 42 represents portions of thelead body that reside in vessels that lead to the heart. The distalregion 46 represents portions of the lead body that reside within theheart, and generally includes at least one of the electrodes 116. Thelead tip region 46 generally represents the distal end of the lead body110 which may include passive or active lead fixation member 36. Theregions illustrated in FIG. 2 can vary in length and/or position on thelead body depending on the type and size of the medical electricaldevice 100, the intended treatment and/or the intended implantationprocedure.

According to some embodiments of the present invention, the Shorehardness of each of at least regions 40, 42, and 44 differs. In oneembodiment, the Shore hardness of the regions 40, 42, and 44 decreasesalong the length of the lead body 110 in a direction from the proximalend 112 to the distal end 114 of the lead body 110 such that theproximal region 40 has a Shore hardness that is greater than the Shorehardness of the distal region 44, and the middle region 42 has a Shorehardness that is less than the Shore hardness of the proximal region 40and greater than the Shore hardness of the distal region 44. In oneembodiment, the regions 40, 42, 44 form discrete regions of decreasingShore hardness. In another embodiment, the Shore hardness can decreasegradually and continuously from the proximal region 40 to the tip region44 of the lead body 110. In one embodiment the Shore hardness of thelead body is about 75D at the proximal region 40 of the lead body 110and 45A the distal region 44 including the tip region 46 of the leadbody 110. In further embodiments, the Shore hardness of the proximalregion 40 ranges from about 85A to about 100A, the Shore hardness of themiddle region 42 ranges from about 60A to about 85A and the Shorehardness of the distal region 46 ranges from about 30A to about 70A.

There are a number of approaches for varying the Shore hardness of thelead body along its length. In one embodiment, the Shore hardness of thepolymeric material can be varied by extruding a lead body having asingle unitary construction. In other embodiments, multiple segments canbe separately formed and bonded together using, for example, heat and/orlaser bonding/fusion and/or medical adhesive.

In some embodiments, a mix or volume ratio of the polymeric materialused to form at least one portion (proximal 40 and/or middle 42) of themulti-lumen lead body 110 can be varied during an extrusion process. Inthis embodiment, polymeric materials having different durometers areblended together and then extruded to form the different portions of thelead body 110. In one embodiment, polyisobutylene polyurethane copolymermaterials having different hard to soft segment ratios Shore hardnessvalues can be blended together in different ratios and extruded to formthe different portions of the lead body 110, having different Shorehardness values. In another embodiment, two or more polyisobutylenepolyurethane copolymer materials having different soft and/or hardsegments can be blended. In a further embodiment, a polyisobutylenepolyurethane copolymer material can be blended with a differentpolymeric material to form one or more portions of the lead body 110.

During the extrusion process, a volume percent of a stiffer polymericmaterial (Polymer A) in the polymeric material blend changes from amaximum amount in the proximal portion 40 of the lead body to a minimumamount in the middle portion 42 of the lead body during extrusion of thelead body 110. Similarly, the volume percent of the softer polymericmaterial (Polymer B) in the polymeric blend changes from a minimumamount in the proximal portion 40 to a maximum amount in the middleportion of the lead body 110. In one embodiment, the durometer ofPolymer A ranges from about 80A to about 100A, and the durometer ofPolymer B ranges from about 25A to about 40A. In one embodiment, thevolume ratio of Polymer A to Polymer B in the blend used to formproximal portion 40 of the lead body 110 ranges from about 75:25 toabout 99:1. In one embodiment, the blend used to extrude the proximalportion 40 contains approximately 100% of Polymer A. In anotherembodiment, the volume ratio of Polymer A to Polymer B used to form amiddle portion 42 of the lead body 110 ranges from about 35:65 to about75:25.

In some embodiments, the distal portion and/or tip region of themulti-lumen lead body 110 can also be extruded and a mix or volume ratioof polymeric material used to form the distal and/or tip portions of thelead body 110 varied to vary the durometer in the distal and/or tipportions 44, 46 of the lead body 110.

In other embodiments, at least two lead body portions are separatelymanufactured (i.e., extruded or molded) and then connected to form thelead body 110. Connection can be achieved by overlapping the portions anapplying an adhesive or by heat fusing to components with little or nooverlapping portion.

FIG. 3A is an illustration of a polymeric lead component 111 (e.g., anelongated tubular component, elongated multi-lumen extrusion, etc.)according to another embodiment having a proximal end 112 and a distalend 114. The polymeric lead component 111 contains an atraumatic tipportion 115 and a main lead portion 119, each of which may contain apolyisobutylene urethane copolymer. The atraumatic tip portion 115 mayrange, for example, from 1 to 2.5 to 5 to 12 cm in length, with the mainlead portion 119 constituting the remainder of the length of the leadcomponent 111 ranging from about 5 to 125 cm (from about 5 cm to 10 cmto 20 cm to 30 cm to 40 cm to 50 cm to 60 cm to 70 cm to 80 cm to 90 cmto 95 cm to 100 cm to 110 cm to 125 cm) in length, depending on leadtype). The atraumatic tip portion 115 is relatively soft, having a Shorehardness ranging, for example, from 30A to 80A (e.g., from 30A to 40A to50A to 52.5A to 55A to 57.5A to 60A to 62.5A to 65A to 67.5A to 70A to72.5A to 75A to 77.5A to 80A). The main lead portion 119, on the otherhand, is relatively hard to provide abrasion resistance and pushability,among other characteristics, having a Shore hardness ranging, forexample, from 75A to 100A (e.g., from 75A to 85A to 90A to 92.5A to 95Ato 97.5A to 100A).

More particularly the lead component 111 such as that shown in FIG. 3Amay have a Shore hardness value of about 50A to 70A at a position thatis 1 cm from the distal end (corresponding to a point within theatraumatic portion 115), and may have a Shore hardness value of about90-A to 100A in the center of the lead component 111 (corresponding to apoint within the main lead portion 119).

By providing portions with different Shore hardness values, optimizedlead properties can be achieved. Generally, it is beneficial to have arelative harder main lead body and a relatively soft tip. The harderlead body provides for improved pushability and torque while the softtip provide for improved maneuverability and lower pressure at thefixation site.

FIG. 3B also is an illustration of a polymeric lead component 111 (e.g.,an elongated tubular component, elongated multi-lumen extrusion, etc.)having a proximal end 112 and a distal end 114. As with FIG. 3A, thepolymeric lead component 111 of FIG. 3B includes an atraumatic tipportion 115 and a main lead portion 119. FIG. 3B further includes aproximal portion 117, which is designed, inter alia, to strike a balancebetween abrasion resistance and flexibility (e.g. for winding the leadinto the pocket during implantation). The proximal portion 117 mayrange, for example, from 10 to 15 cm in length. The proximal portion 117in this embodiment has a Shore hardness ranging from 80A to 98A (e.g.,from 80A to 82.5A to 85A to 87.5A to 90A to 92.5A to 95A to 98A), and incertain embodiments, ranging from 80A to 90A (e.g., from 80A to 82.5A to85A to 87.5A to 90A) for enhanced flexibility of the portion of the leadthat extends from the implanted pacemaker can.

As a specific example a lead component 111 such as that illustrated inFIG. 3B may have a Shore hardness value of about 80A to 90A at aposition that is 5 cm from the proximal end (corresponding to a pointwithin the proximal portion 119), may have a Shore hardness value ofabout 50A to 70A at a position that is 1 cm from the distal end(corresponding to a point within the atraumatic tip portion 115), and amay have a Shore hardness value of about 90A to 100A at a position thatis 10 cm from the distal end (corresponding to a point within the mainlead portion 119).

FIG. 3C is an illustration of a polymeric lead component 111 (e.g., anelongated tubular component, elongated multi-lumen extrusion, etc.)having a proximal end 112 and a distal end 114. As with FIG. 3B, thepolymeric lead component 111 of FIG. 3C includes an atraumatic tipportion 115, a main lead portion 119, and a proximal portion 117. FIG.3C further includes a suture sleeve portion 118, which is designed toprovide clavicle/first rib crush resistance at the venous transitionzone. The atraumatic tip portion 115 and the proximal portion 117 mayhave the above-described lengths and Shore hardness values. The suturesleeve portion 118 may range, for example, from 7.5 to 12 cm in length.The suture sleeve portion 118 in this embodiment has a Shore hardnessranging from 70A to 85A (e.g., from 70A to 72.5A to 75A to 77.5A to 80Ato 82.5A to 85A), and in certain embodiments ranging from 70A to 80A(e.g., from 70A to 72.5A to 75A to 77.5A to 80A) for enhanced crushresistance. The main lead portion 119 in FIG. 3C may have the aboveShore hardness values and may constitute the remainder of the leadcomponent 111 length not taken up by the atraumatic tip portion 115, theproximal portion 117 and the suture sleeve portion 118 (e.g., the mainlead portion 119 may range from about 10 cm to 20 cm to 30 cm to 40 cmto 50 cm to 60 cm to 70 cm to 80 cm in length, depending on lead type).

As a specific example a lead component 111 such as that shown in FIG. 3Cmay have a Shore hardness value of about 80A to 90A at a position thatis 20 cm from the proximal end (corresponding to a point within theproximal portion 119), may have a Shore hardness value of about 70A-80Aat a position that is 10 cm from the proximal end (corresponding to apoint within the suture sleeve portion 118), may have a Shore hardnessvalue of about 50A to 70A at a position that is 1 cm from the distal end(corresponding to a point within the atraumatic portion 115), and a mayhave a Shore hardness value of about 90A to 100 A at a position that is10 cm from the distal end (corresponding to a point within the main leadportion 119).

In addition to optimizing the Shore hardness of portions of thepolymeric lead component 111, the flexural modulus of these portions canalso be optimized. In one embodiment, the main lead body portion 119 hasa flexural modulus of about 4000 to 10,000 psi, the atraumatic tipportion has a flexural modulus of about 1000 to 5000 psi and theproximal portion 119 has a flexural modulus of about 4000 to 10,000 psi.

Each polymeric lead component 111 of FIGS. 3A-C may be formed fromdiscrete polymeric components that correspond to portions 115, 117, 118and 119. For example, such discrete components may be formed separately(e.g., by extrusion) and bonded to one another (e.g., by bonding with anadhesive, thermal fusion, etc.) to form the polymeric lead component111. For example, discrete components corresponding to the atraumatictip portion 115 and the main lead portion 119 may be bonded to oneanother to form the polymeric lead component 111 of FIG. 3A. As anotherexample, discrete components corresponding to the atraumatic tip portion115, the main lead portion 119 and the proximal portion 117 may bebonded to one another to form the polymeric lead component 111 of FIG.33B. As yet another example, discrete components corresponding to theatraumatic tip portion 115, the main lead portion 119, the suture sleeveportion 118 and the proximal portion 117 may be bonded to one another toform the polymeric lead component 111 of FIG. 3C. The use of suchdiscrete components can be used to form lead components 111 with abrupttransitions between the above described hardness ranges (i.e.,transitions of 1 mm or less).

Alternatively, the polymeric composition may change continuously betweenthe portions 115, 117, 118 and 119 of the polymeric lead component 111(e.g., by forming a continuous tubular or multi-lumen extrusion in whichthe composition of the material being extruded is changed during thecourse of extrusion). In such embodiments, lead components 111 withgradual transitions between the above described hardness ranges (i.e.,transitions of greater than 1 mm, more typically greater than 1 cm) maybe formed.

If desired, each lead component 111 of FIGS. 3A-3C may be provided witha proximal terminal of high Shore hardness (not shown). For example sucha proximal terminal may range from 2.5 to 5 cm in length and may rangein Shore hardness from 60D to 70D to 80D to 90D, more preferably about75D. Such a proximal terminal may be formed from a polyurethane withratio of SS:HS between 60:40 to 30:70, more preferably between 60:40 to45:55 and bonded to the lead component 111 (e.g., by thermoplasticbonding, by using a suitable adhesive, etc.).

The polyisobutylene-based copolymers described herein may be employed inconjunction with various lead designs. For example, FIG. 4A is aschematic longitudinal cross sectional view of an insulated(non-electrode) portion of a medical lead 110 in accordance with theinvention. The portion of the lead shown includes a first coiledconductor 130 and a second coiled conductor 132 disposed in a co-radialarrangement with one another. An advantage of a coiled configuration forthe conductors 130, 132 is that the various types of movementsexperienced by the lead in vivo are converted into torsion, which themetals that are typically used to form the coils can readily tolerate.The coiled conductors 130, 132 may be made, for example, of stainlesssteel, Elgiloy, or MP35N, among other suitable conductive materials. Thecoiled conductors 130, 132 are disposed within a tubular insulationlayer 120, which may be formed from polyisobutylene-based copolymers asdescribed herein. The tubular insulation layer 120 acts to chemically,mechanically and electrically insulate the coiled conductors from theexternal environment and can also provide the lead with desirablemechanical characteristics such as flexibility, crush resistance,torqueability, and abrasion resistance, which characteristics may varyalong the length of the layer 120. For example, the tubular insulationlayer 120 may vary in Shore hardness along its length as described inany of FIGS. 3A-3C above, among other possibilities.

Such a tubular insulation layer 120 may be, for example, solvent coatedover the coiled conductors 130,132, extruded over the coiled conductors130,132, or first extruded and then disposed over the coiled conductors130,132, among other possibilities. In the latter case, the pre-formedtubular insulation layer 120 may be bonded to insulating materialprovided on the coiled conductors 130, 132 (not shown) by a suitableelevated temperature process such as laser bonding (where the insulatingmaterial on the conductors is a thermoplastic material).

In another embodiment, the tubular insulation layer 120 can include twoor more layers of polymeric material, which can form two or more coaxialtubular material regions as shown in FIG. 4B. The tubular insulationlayer 120 includes two coaxial tubular material regions 120 a and 120 b.The two coaxial tubular material regions 120 a and 120 can be formedfrom the same or different materials. For example, in one embodiment,the outer material region 120 a can be formed from a polyisobutyleneurethane copolymers such as described above according to the variousembodiments and the inner material region 120 b can be formed from adifferent material such as conventional polyurethanes, silicone rubbers,SIBS (styrene/isobutylene/styrene copolymers), and other polymers usefulin lead body construction known to those of skill in the art. In anotherembodiment, both the inner and outer tubular material regions 120 a and120 b can be formed from a polyisobutylene urethane copolymer such asdescribed above according to the various embodiments.

In some embodiments, the outer material region 120 a can be solventcoated over the inner material region 80 b, co-extruded over the innermaterial region 120 b, co-extruded with the inner material region 120 b,or first extruded and then inserted over the inner material region 120b, among other possibilities. In some embodiments, the outer materialregion 120 a can be fused to the inner material region 120 b by asuitable elevated temperature process such as, for example, a laserbonding process or a thermal bonding process. The use of laser bondingcan create the potential for high speed manufacturing of leads, reducedassembly time and/or improved production yield.

According to yet another embodiment, as shown in FIG. 4C, the lead body110 can include three coaxial tubular material regions 120 a, 120 b and120 c. Each of the three co-axial tubular can be formed from the same ordifferent materials. For example, in one embodiment, the inner and outermaterial regions 120 a and 120 c can be formed from, for example, apolyisobutylene urethane, urea or urethane/urea copolymer provided inaccordance with the various embodiments of the present invention and theintervening region 120 b can include a non-polyisobutylene urethane,urea or urethane/urea copolymer containing material. In anotherembodiment, only the outer material region 120 is formed from apolyisobutylene urethane, urea or urethane/urea copolymer-containingmaterial.

Like FIG. 4, FIG. 6 is a schematic longitudinal cross sectional view ofan insulated portion of a medical lead 110 in accordance with theinvention that includes first and second coiled conductors 130, 132.Unlike FIG. 4, the first and second coiled conductors 130,132 in FIG. 6are disposed in a co-axial (rather than co-radial) arrangement with oneanother. An outer tubular insulation layer 120 is disposed over theouter coiled conductor 130. Like the tubular insulation layer of FIG. 4,the outer tubular insulation layer 120 of FIG. 6 may be formed from apolyisobutylene-based copolymer as described herein. The outer tubularinsulation layer 120 may vary in Shore hardness along its length, forexample, as described in FIGS. 3A-3C, among other possibilities. Theinner coiled conductor 132 is provided with a further tubular insulationlayer 122, which acts to insulate the coiled conductor 132 from theexternal environment (and from the outer coiled conductor 130 as well).The inner tubular insulation layer 122 may also be formed, for example,from a polyisobutylene urethane copolymer as described herein.Alternatively, a soft silicone material (e.g., 50A Shore hardness) maybe used to form the inner tubular insulation layer 122 so as to haveminimal impact on the mechanical properties of the lead.

The outer tubular insulation layer 120 of FIG. 6 can also comprise twoor more material regions, for example, two or more layers of material,which may form two or more coaxial tubular material regions. Specificexamples of two-material and three-material regions suitable for use inthe outer tubular insulation layer 120 of FIG. 6 are described inconjunction with FIGS. 4B and 4C above.

FIG. 7A is a schematic longitudinal cross sectional view illustrating anembodiment which includes an insulated (non-electrode) portion 100 a anda non-insulated (electrode) portion 100 b of a medical lead 110. Theportion of the lead 110 shown includes a polymer-containing innerelongated member 140. Disposed over the right-hand portion 100 b of theinner elongated member 140 is a coiled conductor 130 which may act, forexample, as a shocking/defibrillation electrode for the medical lead110. Because it acts as an electrode, the coiled conductor 130 is eitheruncoated or coated with a conductive layer (e.g., a layer of iridiumoxide, etc.). Disposed over the left-hand portion 100 a of the innerelongated member 140 is a tubular covering 120, which acts to smooth thetransition between the non-electrode portion 100 a and the electrodeportion 100 b (i.e., the tubular covering 120 is provided to create acontinuous diameter for the device). For example, the thickness of thetubular covering 120 can be the same as the diameter of the conductorforming the coil 130, such that the maximum diameter of portion 100 amatches that of portion 100 b. (In addition to ensuring a smooth thetransition between the electrode and non-electrode bearing portions 100b, 100 a, the tubular covering 120 can also assist in insulating anyconductor(s) lying within the inner elongated member 140, and mayimprove the mechanical characteristics of the lead.).

FIG. 7B is a cross section of the device of FIG. 7A, taken along lineB-B, and shows a two-lumen inner elongated member 140 with outer tubularinsulation layer 120. The lumens of the inner elongated member 140 mayaccommodate, for example, a guide wire and a conductor, two conductors,etc. Other configurations, including inner elongated members with one,four, five, six, seven, eight, etc. lumens are also possible.

The inner elongated member 140 of the device of FIGS. 7A-7B may beformed, for example, using a polyisobutylene-based copolymer asdescribed herein. The inner elongated member 140 may vary in Shorehardness along its length, for example, as described in FIGS. 2A-2C,among other possibilities. An advantage associated with the use ofpolyisobutylene-based copolymers as described herein for forming innerelongated member 140 is that the member 140 can be extruded via athermoplastic process. Similarly, the outer tubular insulation layer 120may also be formed, for example, using a polyisobutylene-based copolymeras described herein. The outer tubular insulation layer 120 may alsovary in Shore hardness along its length, for example, as described inFIGS. 2A-2C, among other possibilities. The outer tubular insulationlayer 120 may be, for example, solvent coated over the inner elongatedmember 140, extruded over the inner elongated member 140, co-extrudedwith the inner elongated member 140, or first extruded and then insertedover the inner elongated member 140, among other possibilities.

An advantage associated with the use of polyisobutylene-based copolymersas described herein for forming both the outer tubular insulation layer120 and the inner elongated member 140 is that the tubular insulationlayer 120 can be fused to the inner elongated member 140 by a suitableelevated temperature process, for instance, a laser bonding process.Such a process may be used, for example, to create a ring-shapedthermally fused region 150 as shown in FIG. 4A (e.g., by rotating thedevice under laser irradiation). By extending the fused region entirelyaround the circumference of device, an effective seal is formed betweenthe tubular insulation layer 120 and inner elongated member 140. Ofcourse a laser bonding process can produce thermally fused regions ofvarious shapes in addition to ring shaped regions. For example, thetubular covering 120 can be “spot-fused” to the inner elongated member140 at various locations (in a process analogous to spot-welding) toprevent unacceptable levels of movement between the tubular covering 120and inner elongated member 140 during implantation.

FIG. 8 is a partial schematic view of a polymeric (non-electrode)portion of a medical lead 110 in accordance with the invention. Theportion of the lead shown includes a single loop 110 s of a spiral.Additional loops may be provided as desired. Typically, such a spiralwill typically range from 1.5 to 5 cm in diameter.

FIG. 9 is an enlarged schematic cross-sectional view taken along lineB-B of FIG. 6 and illustrates a first coiled conductor 130 and a secondcoiled conductor 132 disposed in a co-radial arrangement with oneanother (analogous to FIG. 4). The coiled conductors 130,132 aredisposed within a tubular insulation structure, half of which is formedfrom a first material 120 a and half of which is formed from a secondmaterial 120 b. Each of the first and second materials 120 a, 120 b maybe formed from polyisobutylene-based copolymers as described herein. Thefirst material 120 a corresponds to the surface 110 so of the spiral 110s that faces radially outward from the spiral 110 s. First material 120a is a relatively high hardness material, for example, one having aShore hardness ranging from 90A to 95A to 100A. The second material 120b corresponds to the surface 110 si of the spiral 110 s that facesradially inward. Second material 120 b is a relatively low hardnessmaterial, for example, one having a Shore hardness ranging from 50A to60A to 70A to 80A to 90A to 100A.

Such a two-material lead insulation may be provided only in the area ofthe spiral 110 s, or it may be provided along the entire length of thelead. The spiral 110 s may correspond, for instance, to a portion of aleft ventricular lead, or a heart failure lead that is to be positionedin the coronary sinus and may allow the lead to be passively fixedwithin the body. In such embodiments, the spiral will typically rangefrom 2 to 5 cm in diameter and will be formed from the portion of thelead that lies between 1 and 10 cm from the distal end of the lead.

FIG. 10 is an alternative enlarged schematic cross-sectional view takenalong line B-B of FIG. 8 and illustrates a first conductor 130 and asecond conductor 132 disposed in two lumens of a multi-lumen elongatedmember, half of which is formed from a first material 120 a and half ofwhich is formed from a second material 120 b, each of which may beformed from polyisobutylene-based copolymers as described herein. Thefirst material 120 a corresponds to the surface 110 so of the spiral 110s that faces radially outward. Material 120 a is a relatively highhardness material, for example, one having Shore hardness values likethat of material 120 a in FIG. 7. The second material 120 b correspondsto the surface 110 si of the spiral 110 s that faces radially inward.Material 120 b is relatively low hardness material, for example, onehaving Shore hardness values like that of material 120 b in FIG. 9.

Material regions 120 a and 120 b in FIG. 9 and FIG. 10 or may be formedseparately (e.g., by extrusion, molding, etc.) and bonded to one another(e.g., by thermoplastic bonding, by using a suitable adhesive, etc.).Alternatively, the material regions 120 a and 120 b may besimultaneously formed in a single extrusion operation.

The spiral of FIGS. 8-10 may be established, for example, by firstmechanically forcing the lead 110 into a shape that includes the spiral110 s, then heating the lead to a suitable temperature (e.g., betweenthe softening and melting temps of the materials 110 a and 110 b),followed by cooling the lead, thereby allowing the lead to memorize thecoiled shape. For instance, the lead may be heated to between 140 and200° C., depending on the composition of the lead, among otherpossibilities. In other embodiments, a spiral may be formed usingmolding techniques. A spiral may be established in vivo by disposing thelead over a relatively stiff guide wire which holds the lead in asubstantially linear configuration. Upon removal of the guide wire thelead changes in shape in an effort to recover its memorized spiralshape.

FIG. 11 is an end cross-sectional view of the lead body 110 according toyet another embodiment of the present invention. As shown in FIG. 11,the insulative lead body 110 includes a plurality of cable conductors130, each having a plurality of conductive filaments 131. The filaments131 may be separately insulated from one another. According to oneembodiment the cable conductors 130 can include at least one layer ofinsulation 134 provided over their outer periphery. In one embodiment,the outer tubular insulation 136 forming the lead body 110 can beco-extruded along with the cable conductors 130 or the individualfilaments 131 forming the cable conductors 130. In another embodiment,the outer insulation 136 can be molded around the cable conductors 130.In one embodiment, the outer tubular insulation 136 can be formed from apolyisobutylene urethane copolymer such as described above according tothe various embodiments. In a further embodiment, the insulation layersurrounding each of the individual cable conductors 130 also can beformed form a polyisobutylene urethane copolymer such as describedabove.

FIGS. 12A and 12B are cross-section views of a lead body 110 accordingto still other embodiments of the present invention. As shown in FIG.12A, the lead body 110 is formed such that includes four lumens 152,although any number of lumens can be provided. In one embodiment, thelead body 110 is formed from a polyisobutylene urethane, urea orurethane/urea copolymer such as described above according to the variousembodiments and can be either extruded or molded. As shown in FIG. 12B,the lead body 110 includes an inner core member 154 including multiplelumens 152 and at least outer tubular insulation layer 156. In someembodiments, both the inner core member 154 and the outer tubularinsulation layer 156 can be formed from a polyisobutylene urethane, ureaor urethane/urea copolymer such as described above. In anotherembodiment, only the outer tubular insulation layer 156 is formed from apolyisobutylene urethane, urea or urethane/urea copolymer.

According to some embodiments, various additional lead body componentscan be formed from a polyisobutylene urethane copolymers. For example, apolyisobutylene urethane copolymer having a high durometer (e.g. greaterthan about 85A) can be used to form those components traditionallyconstructed from material such as PEEK or Tecothane. In anotherembodiment, a polyisobutylene urethane copolymer can be molded over anexisting lead body component. Such lead components include, but are notlimited to: lead terminals, terminal pins, lead tips, portions of theheader, and others. In another embodiment, a polyisobutylene urethanecopolymer having a low durometer (e.g. less than about 60A) can be usedto fabricate lead body components traditionally fabricated usingsilicone rubbers including but limited to: O-rings, seals, low traumatictips or tip heads. In still another embodiment, a polyisobutyleneurethane copolymer such as described above according to the variousembodiments of the present invention can be used to construct variousportions of a pulse generator to which the lead is connected includingportions of the connectors and/or headers.

In certain embodiments of the invention, the outer surfaces of the leadbody and/or lead body components formed from polyisobutylene urethanecopolymers can be treated to increase their lubricity. For example, inone embodiment, the outer surfaces can be coated with a parylene layeror plasma grafted with a biocompatible monomer for this purpose,examples of which include hexamethylene disilazane, C3F8(octafluoropropane), polyvinyl pyrollidone, trifluoromethane,octafluorocyclobutane and tetraglyme among others. For example,modification of the outer surface via plasma grafting with tetraglymeproduces a polyethylene glycol like surface. Additional exemplarycompounds and methods of treating the surfaces of the lead body and/orlead body components are shown and described in U.S. ProvisionalApplication No. 61/098,450 filed on Sep. 19, 2008 entitled SURFACEMODIFICATION TO IMPROVE LUBRICITY, ABRASION RESISTANCE AND TEMPERATURERESILIENCE OF LEADS which is incorporated herein by reference in itsentirety.

According to some embodiments, the polyisobutylene urethane copolymersdescribed above according to the various embodiments also can be used toprovide a thin film covering over the outer surface of an electrode.FIG. 11 is a longitudinal cross sectional view of a portion of the leadbody 12 including a coiled electrode 200 according to variousembodiments of the present invention. The coiled electrode 200 is formedfrom at least one conductive filar 206 and has an outer surface 210extending from a first end 212 to a second end 214. According to oneembodiment, the coiled electrode 180 includes a polymeric cover 220disposed over the outer surface 210 of the electrode 200 such that itextends from at least the first end 212 to the second end 214. In afurther embodiment, the polymeric cover 220 can extend beyond the firstand/or second ends 212, 214 of the coiled electrode. In one embodiment,the polymeric cover 220 has sufficient porosity so as to promoteconductivity. In a further embodiment, the polymeric cover 220 has adegree of porosity that is large enough to support conductivity whenwetted with an appropriate ionic fluid, but small enough to preventtissue ingrowth. As such, a polymeric cover 220 formed from apolyisobutylene urethane, urea or urethane/urea copolymer such asdescribed above according to the various embodiments may be used inplace of the traditional GORE® electrode coverings used to cover coileddefibrillation electrodes.

The polymeric covering 220 includes one or more layers of a thin film224 formed form a polyisobutylene urethane, urea or urethane/ureacopolymer described above according to various embodiments of thepresent invention. Multiple layers of the thin film 224 can be wrappedabout the outer surface 210 of the electrode 200 to achieve a desiredthickness. A helical wrap or a cylindrical wrapping technique can beemployed to wrap multiple layers of the polymeric thin film 224 to formthe polymeric cover 220. In one embodiment, the polymeric covering 220can be bonded to the outer surface of the lead body 12 which may alsocomprise the same or similar polymeric material. In another embodiment,the polymeric cover 220 can be bonded to a polymeric filler materialthat is disposed between gaps formed between the windings of thefilar(s) used to form the coiled electrode. The polymeric fillermaterial also can be formed from the same or similar material as thepolymeric covering 220.

The thin film 224 used to form the individual layers of the polymericcover 220 can be formed using a variety of techniques known to those ofskill in the art. According to one embodiment of the present invention,an electrospinning technique can be used to form the thin film 224.Electrospinning of liquids and/or solutions capable of forming fibers,is known and is described, for example, U.S. Pat. No. 4,043,331 which ishereby incorporated by reference herein. Electrospinning produces acontinuous web or matrix of fibers. In one embodiment, the fibrousmatrix forming the thin film 224 can be directly onto the outer surface210 of the electrode 200. In another embodiment, the fibrous matrixforming the thin film 224 first can be formed on a substrate, and thenwrapped about or slid over the outer surface 220 of the electrode asdescribed above. Due to the small diameters of the electrospun fibers,electrospun fiber matrices inherently possess a very high surface areaand a small pore size. In a further embodiment, the fibrous matrix canbe formed such that has a sufficient degree of porosity so as to promoteconductivity.

In addition to the polyisobutylene urethane copolymers disclosed herein,the polymeric components for use in the medical devices of the presentinvention may optionally contain one or more supplemental agents. Forexample, in some embodiments, an organically modified silicate isprovided as a supplemental agent. Such an agent may act to create atortuous pathway for moisture thereby decreasing the moisturepermeability of the polymeric component. Moreover, such silicates maymaintain the strength and increase the modulus of the polymericcomponent. Supplemental agents further include agents such as alumina,silver nanoparticles, and silicate/alumina/silver nanoparticlecomposites and therapeutic agents (discussed in more detail below).

In embodiments where one or more therapeutic agents are provided, theymay be positioned beneath, blended with, or attached to (e.g.,covalently or non-covalently bound to) polymeric regions (e.g., leadcomponents) in accordance with the invention. “Therapeutic agents,”“drugs,” “pharmaceutically active agents,” “pharmaceutically activematerials,” and other related terms may be used interchangeably herein.

A variety of therapeutic agents can be employed in conjunction with thepresent invention including the following among others: (a)anti-inflammatory agents such as dexamethasone, prednisolone,corticosterone, budesonide, estrogen, sulfasalazine and mesalamine, (b)antimicrobial agents such as triclosan, cephalosporins, aminoglycosidesand nitrofurantoin; (c) anesthetic agents such as lidocaine, bupivacaineand ropivacaine, (d) anti-proliferative agents such as paclitaxel, (e)immunosuppressants such as sirolimus, biolimus and everolimus, (f)anti-thromobogenic agents such as heparin, and (g) growth factors suchas VEGF.

Where a therapeutic agent is present, a wide range of loadings may beused in conjunction with the medical devices of the present invention.Typical therapeutic agent loadings range, for example, from than 1 wt %or less to 2 wt % to 5 wt % to 10 wt % to 25 wt % or more of thepolymeric region (e.g., lead component).

Moreover, in some embodiments, a part of the lead body or the completelead body can be further coated with a lubricious coating, typicallyformed from a hydrophilic polymer or other material (e.g., poly(vinylpyrrolidone), polyethylene/oligoethylene, polyHEMA, polytetraglyme,hyalorunic acid and its derivatives, chitosan and its derivatives,etc.), which material may be crosslinked, to reduce coefficient offriction.

Numerous techniques are available for forming polymeric regions inaccordance with the present invention.

For example, where the polyisobutylene urethane copolymers of theinvention have thermoplastic characteristics, a variety of standardthermoplastic processing techniques may be used to form polymericregions from the same. Using these techniques, a polymeric region can beformed, for instance, by (a) first providing a melt that containspolymer(s) and any other optional agents such as silicates, therapeuticagents, and so forth, and (b) subsequently cooling the melt. Examples ofthermoplastic processing techniques include compression molding,injection molding, blow molding, spraying, vacuum forming, calendaring,extrusion into sheets, fibers, rods, tubes and other cross-sectionalprofiles of various lengths, and combinations of these processes. Usingthese and other thermoplastic processing techniques, entire devices orportions thereof (e.g., device components) can be made.

Other processing techniques besides thermoplastic processing techniquesmay also be used to form the polymeric regions of the present invention,including solvent-based techniques. Using these techniques, polymericregions can be formed, for instance, by (a) first providing a solutionor dispersion that contains polymer(s) and any optional agents such astherapeutic agents, silicates and so forth, and (b) subsequentlyremoving the solvent. The solvent that is ultimately selected willcontain one or more solvent species, which are generally selected basedon their ability to dissolve the polymer(s) that form the polymericregion, in addition to other factors, including drying rate, surfacetension, etc. In certain embodiments, the solvent is selected based onits ability to dissolve or disperse the optional agents, if any. Thus,optional agents such as therapeutic agents, silicates, and so forth maybe dissolved or dispersed in the coating solution. Solvent-basedtechniques include, but are not limited to, solvent casting techniques,spin coating techniques, web coating techniques, spraying techniques,dipping techniques, techniques involving coating via mechanicalsuspension including air suspension, ink jet techniques, electrostatictechniques, and combinations of these processes.

In some embodiments of the invention, a polymer containing solution(where solvent-based processing is employed) or a polymer containingmelt (where thermoplastic processing is employed) is applied to asubstrate to form a polymeric region. For example, the substrate cancorrespond to all or a portion of an implantable medical device to whicha polymeric coating is applied, for example, by spraying, extrusion, andso forth. The substrate can also be, for example, a template, such as amold, from which the polymeric region is removed after solidification.In other embodiments, for example, extrusion and co-extrusiontechniques, one or more polymeric regions are formed without the aid ofa substrate. In a specific example, an entire medical device componentis extruded. In another example, a polymeric coating layer isco-extruded along with and underlying medical device component. Inanother example, a polymeric tube is extruded which is then assembledover a medical device substrate (e.g., on an electrical lead, either asan electrically insulating or electrically non-insulating jacket).

As noted above, in various embodiments of the invention, a medical leadcomponent (e.g., an elongated tubular component, elongated multi-lumenextrusion, etc.) is formed which varies in hardness or stiffness alongits length. In some embodiments, such a component may be formed, forexample, from previously formed components of differing hardness thatare bonded to one another (e.g., by thermoplastic bonding, by using asuitable adhesive, etc.). In some embodiments, such a component may beformed by an extrusion operation in which the composition of theextruded component is varied during the course of the extrusionoperation.

One example of such an extrusion operation is one in which previouslyformed polymers are fed into a single die from multiple polymer sources(e.g., using multiple feed screws), with each polymer source supplying apolymer that has a hardness that differs from the polymers supplied bythe other sources. By varying the relative amount of copolymer that issupplied by each polymer source during the course of the extrusion, anextruded component of varying hardness (e.g., along its length, acrossits cross-section, etc.) can be produced.

Another example of such an extrusion operation is a reactive extrusionoperation in which reactants (e.g., a polyisobutylene diol, a polyetherdiol such as polytetramethylene oxide diol and/or polyhexamethyleneoxide diol, 1,4-butanediol diol, diisocyanate such as MDI and a suitablecatalyst) are fed into an extruder using suitable flow controllers.Extruders of this type are described, for example, in U.S. Pat. No.3,642,964 to Rausch Jr. et al. and U.S. Pat. No. 6,627,724 to Meijs etal. The extruder is operated at a temperature which promotes thepolymerization process. The relative feed rates of each of the reactantscan be varied over time to create an extrusion of varying hardness. Theextruded polymer may be post-cured for reaction completion and mayfurther be annealed for stress-relaxation.

EXAMPLES Experimental Materials

PTMO (TERATHANE® 1000 polyether glycol),4,40-methylenebis(phenylisocyanate) (98%), toluene (99%), 1,4-butanediol(99%), hydrogen peroxide solution (30%), cobalt chloride hexahydrate(98%), and Triton® X-100 were used as received from Sigma-Aldrich (St.Louis, Mo.). Sn(Oct)₂ (stannous octoate, Polyscience, Niles, Ill.) andtetra-n-butyl-ammonium bromide (TBAB) (98+%, Alfa Aesar, Ward Hill,Mass.) were used as received. The control samples in this studyconsisted of PELLETHANE™ 2363-55D and PELLETHANE™ 2363-80A, receivedfrom Dow Chemical. Polyurethanes of varying hardness and PIB:PTMOcompositions were synthesized as reported previously and are listed inTable I provided below.

TABLE 1 Polyurethane Nomenclature and Compositions HO—-PIB—OH^(a)HO—PTMO—OH^(b) PTMO wt % Shore A Code (wt % in SS) (wt % in SS) SS:HS(wt:wt) in polymer Hardness 60A 82 80 20 79:21 16 60 60A 91 90 10 79:218 60 80A 73 70 30 65:35 19.5 80 80A 82 80 20 65:35 13 80 80A 91 90 1065:35 6.5 80 100A 82 80 20 60:40 12 100  60A PIB 100   0 79:21 0 60 60A91 90 10 79:21 8 60 SAT ^(a)HO—PIB—OH, M_(n) = 2200 Da. ^(b)HO—PTMO—OH,M_(n) = 1000 Da.

The two-stage process is described for a representative polyisobutyleneurethane copolymer (60A 82) as follows: HO-Allyl-PIB-Allyl-OH(M_(n)=2200 Da, 5.2 g, 2.36 mmol) and PTMO (M_(n)=1000 Da, 1.3 g, 1.3mmol), were dried by azeotropic distillation using dry toluene (10 mL).The mixture was kept at 45° C. for 3 hours under vacuum. Dry toluene (25mL) was added followed by Sn(Oct)₂ (28.3 mg, 0.07 mmol) in toluene. Themixture was heated at 80° C. under a slow stream of dry nitrogen gas.Then MDI (1.76 g, 7.02 mmol) was added to the mixture and the mixturewas stirred vigorously for 30 min. Finally BDO (302 mg, 3.36 mmol) wasadded and the mixture was stirred at 100° C. for 4 hours. The mixturewas cooled to room temperature, poured into a Teflon mold and thesolvent was evaporated at room temperature in air for 48 hours. Finally,the polymer was dried under vacuum at 50° C. for 12 hours. Apolyisobutylene urethane copolymer without PTMO was prepared accordingto a process shown and described in Ojha et al. Syntheses andCharacterization of Novel Biostable Polyisobutylene Based ThermoplasticPolyurethanes Polymer 2009; 50:3448-3457, which is incorporated hereinby reference. The saturated PIB-PTMO polyurethane was synthesized usingHO-propyl-PIB-propyl-OH, prepared using a method shown and described inBela et al. Living Carbocation Polymerization. XX. Synthesis ofAllyl-Telechelic Polyisobutylenes by One-PotPolymerization-Functionalization Polymer. Mater. Sci. Eng. 1988;58:869-872, which is incorporated herein by reference in its entirety.

The polyurethanes were compression molded using a Carver LaboratoryPress model C (Wabash, Ind.) at a load of 16,000 lbs. at 160° C. Theywere molded into thin films ranging in thickness from 0.2 to 0.5 mm andcut into rectangular strips with approximate dimensions of 3 mm in widthand 30 mm in length. The polyurethanes were characterized prior toaccelerated degradation using ¹H NMR and GPC. Some compositions (80A 91,100A, 60A PIB) did not dissolve in the GPC eluent.

Labeling System

In this labeling system the first set of characters describe the Shore Ahardness. The next two numbers denote the ratio of PIB:PTMO. Extraletters denote a polyurethane that is unique to the series ofpolyurethanes tested, such as PIB which indicates exclusively PIB in theSS, or SAT which indicates that the PIB precursor used contained thesaturated hydroxypropyl versus the hydroxyallyl end groups. P55D andP80A refer to PELLETHANE™ 2363-55D and PELLETHANE™ 2363-80A,respectively.

In Vitro Oxidative Treatment

The samples were placed in vials and soaked in a 20% H₂O₂ in aqueous 0.1M CoCl₂ solution and stored at 50° C. The solutions were changed everyother day to ensure a steady concentration of radicals. At time pointsafter 1, 2, 4, 6, and 12 weeks, dedicated samples were removed from theoxidative environment, washed seven times in aqueous 1% TRITON® X-100surfactant solution, five times in ethanol, and five times in distilledwater and dried under vacuum at 80° C. until constant weight.

Characterization

Dry samples were characterized by weight loss, ATR-FTIR spectroscopy,ultimate tensile strength, elongation at break, SEM, and GPC. Theresults of characterization are reported using n=3.

Example 1 Weight Loss

Weights were measured of dry polyurethane films before and afteroxidative treatment on a Sartorius MC1 Analytic AC 210S balance (ElkGrove, Ill.). The weight loss plotted against time is shown in FIG. 14.The PIB-PTMO polyisobutylene urethane copolymers all show very lowweight loss after 12 weeks ranging from values of 6-15% depending on thecomposition. Among the 60A batch, the 90/10 composition showed lowerweight loss of 6% compared to 8% for the 80/20 composition. The 60A 91SAT shows weight loss comparable to the unsaturated 60A 91. Similarly inthe 80A batch, the polyisobutylene urethane copolymers with lower PTMOcontent showed lower weight loss, 15, 10, and 6% for 30, 20, and 10%PTMO, respectively. More specifically, the weight loss could becorrelated to the PTMO content in the polyurethanes.

In FIG. 15 weight loss at 12 weeks versus PTMO content is plotted. Ascan be seen for the PIB-PTMO polyisobutylene urethane copolymers thereis approximately a linear relationship between the weight loss and thePTMO content. This discovery supports the notion that it is thepolyether SS which degrades via MIO and it is these portions which areexcised from the polyurethane. As shown in FIG. 15, 60A 82 showed alower weight loss than expected for its PTMO content. Thepolyisobutylene urethane copolymer which contained only PIB also showeda small weight loss, which fits the plot. Since there is such a largesurface area to volume ratio, we expect to see some small erosion fromthe surface. The PELLETHANE™ control samples showed noticeable weightloss even after 1 week in vitro, and P80A and P55D completely degradedafter ˜7 and 9 weeks, respectively. It is observed that P80A, containingmore SS, loses weight more rapidly than P55D, which is consistent withthe proposed mechanism of oxidation.

Example 2 ATR-FTIR

ATR-FTIR was performed on a Thermo Electron Corporation Nicolet 4700FT-IR instrument (Waltham, Mass.) with a Thermo Electron CorporationSmart Orbit attachment for ATR with a diamond crystal. Thirty-two scanswere averaged to obtain one representative spectrum for each sample. Therespective dry clean polyisobutylene urethane copolymer strip was placedon the crystal, firmly secured using the foot attachment, and scannedfor analysis. The region of interest was between ˜1700 cm⁻¹ and ˜1100cm⁻¹, which includes HS degradation product (˜1650 cm⁻¹), SS degradationmoiety (˜1110 cm⁻¹) and product (˜1170 cm⁻¹) and the normalizedreference peak (˜1410 cm⁻¹).

ATR-FTIR analysis was performed to confirm the presence and progressionof the MIO mechanism. In this mechanism, a hydroxyl radical abstractsa-hydrogen from the polyether segment. The resulting radical may combinewith another chain radical to form a crosslink junction or react withanother hydroxyl radical to form a hemiacetal. The hemiacetal oxidizesto ester which is subsequently hydrolyzed resulting in chain scission.Therefore progression of degradation can be observed by following thedisappearance of the SS ether peak and/or the appearance of thecrosslinking peak. All spectra were normalized to the peak at 1410 cm⁻¹,which corresponds to the aromatic C—C stretch of the hard segment.

The PIB-PTMO polyurethanes all show very small changes in the FTIRspectrum. A representative spectrum, that of 60A 82, is shown in FIG.16. There is no appreciable change in the aliphatic ether C—O—C peak at1110 cm⁻¹ and C—O—C branching peak at ˜1174 cm⁻¹ is absent. However, anincrease in the aliphatic peaks with time is observed (aliphatic CH₂bending at 1470 cm⁻¹, PIB dimethyl wag at 1388 cm⁻¹, and aliphatic CH₂wag at 1365 cm⁻¹). This behavior can be rationalized by migration of PIBsegments to the surface during vacuum drying at 80° C. Since these peaksincrease with time, it is suggested that the PIB is replacing PTMO onthe surface (1-2 μm deep as observed by ATR-FTIR). Together with theweight loss and SEM data shown in FIGS. 14-15 and 24-25 it is concludedthat there is some. PTMO degradation. In these PIB-PTMO polyisobutyleneurethane copolymers cross-linking may be absent since there is not asignificant presence or mobility of PTMO to allow two polymer radicalsto combine before they are otherwise cleaved. Similar results areobserved in the other PIB-PTMO spectra. The 60A 91 SAT batch wasincluded in this study to determine if the unsaturated allyl moiety inthe PIB diol was vulnerable to oxidation. The FTIR spectrum of thepolyisobutylene urethane copolymer using the saturated diol appearsidentical to that of the polyisobutylene urethane copolymer containingunsaturated diol. Additionally the 60A PIB polyisobutylene urethanecopolymer was included to confirm that there is only polyether SSdegradation, and not HS degradation in these polyisobutylene urethanecopolymers. These spectra are shown in FIG. 17. This hypothesis wasconfirmed as the spectrum shown in FIG. 17 shows no change at all. Thereis no change in the PIB peak at 1388 cm⁻¹ or ether peak at 1111 cm⁻¹since there is no polyether to be degraded. There is also no evidence ofHS T2 degradation. Table 2, shown below, lists the IR peaks where trendsof change were observed.

TABLE 2 Assigned ATR-FTIR Spectral Peak Changes Wave Number (cm⁻¹)Proposed Peak Assignment P80A P55D PIB—PTMO 1637 NH₂ aromatic amine X —— 1476 Aliphatic CH₂ bend — — X 1388 PIB CH₃ wag — — X 1365 Aliphaticα—CH₂ wag X X X 1173 C—O—C branching X X — 1110 Aliphatic C—O—C X X —

The PELLETHANE™ samples showed the expected behavior as is consistentwith the weight loss data as well as previous studies. The spectra ofP55D are shown in FIG. 18 The spectrum shown in FIG. 18 exhibits asignificant decrease in the aliphatic C—O—C peak at 1109 cm⁻¹ after 1week, then more slowly until 6 weeks. Concurrently, we observe a rapiddisappearance of the aliphatic a-CH₂ peak at 1364 cm⁻¹ after just 1week. Also the C—O—C branching peak at 1172 cm⁻¹ is observed immediatelyat 1 week, then stays constant in magnitude. As it will be seen later,the PELLETHANE™ samples continued to degrade at a constant, if notaccelerated rate after 1 week, and so an explanation is in order for theIR spectra. ATR-FTIR is a surface characterization technique anddegradation is expected to begin at the surface. Therefore we concludethat the segments vulnerable at the surface are oxidized almostimmediately and deeper oxidation occurs in the following weeks asobserved from the rest of the analyses. The ATR-FTIR spectra of P80A areshown in FIG. 19, and show very similar results. The magnitudes of thedifferences in the ether and crosslinking peaks are different than inP55D. The tensile data indicates (see later) that chain scission had apredominant effect on P55D over crosslinking, whereas P80A was affectedgreatly by both crosslinking and chain scission in turn.

Example 3 GPC

Molecular weights and molecular weight distributions were measured witha Waters HPLC system equipped with a model 510 HPLC pump, model 410differential refractometer, model 441 absorbance detector, onlinemulti-angle laser light scattering (MALLS) detector (Mini-Dawn, WyattTechnology, Santa Barbara, Calif.), Model 712 sample processor, and fiveUltrastyragel GPC columns (Waters, Milford, Mass.) connected in thefollowing series: 500, 103, 104, 105, and 100 Å. A hydrogen bonddisruptor, tetra-n-butyl ammonium bromide (TBAB), was dissolved in THF(2% by weight) and used to dissolve the polyisobutylene urethanecopolymers. The solution of THF:TBAB (98:2, wt:wt) was used as a carriersolvent with a flow rate of 1 mL min⁻¹.

The polyisobutylene urethane copolymer samples were dissolved in thecarrier solvent of THF:TBAB (98:2, wt:wt). However, some compositionscould not be dissolved. Comparison of the GPC results of theas-synthesized polymer and that of compression molded, untreated films(0 weeks), indicates that there is some crosslinking or other thermaldegradation occurring during processing at elevated temperatures.Nevertheless, such minute changes did not seem to affect the propertiesof the polyisobutylene urethane copolymers.

FIG. 20 shows the refractive index traces of P55D. The number averagemolecular weight (M_(n)) shows a decrease from 122 kDa at 0 weeks to 47kDa at 4 weeks, and then 37 kDa at 6 weeks, while the molecular weightdistribution (MWD) increases from 1.6 at 0 weeks to 3.0 at 6 weeks.

In FIG. 21 the refractive index traces of P80A are shown. M_(n) shows aclear trend decreasing from 84 kDa before treatment to 18 kDa at 4 weeksand 14 kDa at 6 weeks. There is a clearly visible rise in some lowmolecular weight degradation product(s) by 4 weeks. Simultaneously thereis an increase in the MWD. These findings are in agreement with theATR-FTIR, weight loss, and tensile results.

GPC refractive index traces are shown FIG. 22 for 60A 91 SAT. The lossin molecular weight is minimal in agreement with the weight loss andtensile data. M_(n) decreases slightly from 130 to 112 kDa after 6weeks, then negligibly to 110 kDa at 12 weeks while the MWD remainedunchanged at 1.6.

Example 4 Mechanical Testing

Tensile testing was performed at room temperature and atmosphericconditions with a 50 lb. load cell on an Instron Model Tensile Tester4400R (Norwood, Mass.) at 50 mm min⁻¹ extension rate until failure.Ultimate tensile strength and elongation at break were recorded.

Tensile strength is plotted as a percentage of the original untreatedsample versus time in FIG. 23. A drastic difference in the plots for thePELLETHANE™ urethane copolymers versus the PIB-PTMO polyisobutyleneurethane copolymers is observed. Additionally, in the PIB-PTMOpolyisobutylene urethane copolymers a minimal decrease in tensilestrength is observed for all samples, although the rate of tensile lossvaries for the different samples. The PIBPTMO polyisobutylene urethanecopolymers show differing losses which are roughly correlated to thePTMO content. Among the 60A batch, the tensile losses from the differentcompositions are comparable. The 12-week data point for the 60A 91 couldnot be obtained because of a poor sample set. Nevertheless, the trendobserved up to 6 weeks follows very closely that of the 60A 91 SAT.Minimal decrease in tensile strength was also observed in the 60A PIBsample, which showed no degradation as evident from weight loss and FTIRstudies, discussed above. This indicates that 1-2 MPa may be withinexperimental error with the load cell and instrument used. Among the 80Abatch the 80/20 composition shows ˜21% drop in tensile strength, whereasthe 90/10 composition shows only a decrease of ˜13%. The 80A 73 sample(not shown here) demonstrated an initial increase in tensile strength,then subsequently a slower decrease. This is attributed to crosslinkinginitially, followed by chain scission consistent with the increasedamount of PTMO in this sample. At this amount of PTMO (19.5% of totalpolyisobutylene urethane copolymer), there are sufficient concentrationof chain radicals such that crosslinking as well as chain scission mayoccur. Although the % tensile strength at 12 weeks is greater than theother PIB-PTMO polyisobutylene urethane copolymers, extrapolation of thedata would predict that the tensile strength 80A 73 would drop moresharply at longer time intervals. P55D shows greater resistance todegradation compared to P80A due to higher crystallinity. Thus the 100A82 composition is expected to have comparable if not better strengththan the 80A 82 composition, yet we see greater tensile drop. This maysuggest that PIB is a better protector of the surface than the hardsegment. Some of the samples actually show inhibition periods whereinthe tensile strength does not begin to decrease until 2, 4, or even 6weeks (esp. 80A 82). The ultimate elongation of the PIB-PTMOpolyisobutylene urethane copolymers did not change significantly overthe course of the treatment. The PELLETHANE™ samples again showedexpected MIO behavior. P55D showed gradual tensile loss over time up to6 weeks, and at 12 weeks there was no sample to test, as the samples hadfractured in vitro. P80A showed an initial increase in tensile strengthafter 1 week, then a rapid decrease and had fractured before 12 weeks.This is explained by crosslinking of the chains initially, with chainscission occurring afterward as was observed with 80A 73. Since ATR-FTIRresults indicate that in P55D crosslinking is also present, it isinferred that chain scission is the dominant oxidative route under theseconditions. It was also observed that the modulus of the PELLETHANE™samples increased with time approximately linearly, indicatingcrosslinking, consistent with the IR data, whereas the modulus of thePIB-PTMO polyisobutylene urethane copolymers remained stable.

Example 5 SEM

Portions of the dry treated films were isolated for SEM analysis.Surface morphology was observed on gold sputter-coated samples using aDenton Vacuum Desk IV Cold Cathode Sputter Coater (Moorestown, N.J.).The samples were sputter-coated for 1.5 min at 25% power, correspondingto a thickness of ˜75 Å of gold. The coated samples were observed usinga JEOL model JSM 7401F field emission scanning electron microscope(Peabody, Mass.). Several representative pictures were taken at 30× and300× magnification.

Representative SEM pictures taken at 300× magnification are shown inFIGS. 24 and 25 Shown in FIG. 24 are the PELLETHANE™ samples, which showthe well observed behavior of surface degradation with treatment time.The surface density of cracks increases with time, and the visualinspection affirms the previous data as well. In FIG. 25, scanningelectron micrographs of the 80/20 compositions are shown with differenthardness to depict the effect of HS on the surface morphology. Theresponses of these polyisobutylene urethane copolymers to degradationare certainly different than the PELLETHANE™, but a trend of increasingsurface imperfections with increasing SS content can be seen. The 60A 82shows some pitting after 12 weeks, 80A 82 shows less pitting, and 100A82 shows essentially no change in the surface morphology after 12 weeks.Some small holes are often observed in various samples, but these arenot expected to be due to degradation. The same patterns were observedin the 60A PIB samples, which did not degrade; therefore such holes areexpected to be an artifact of the compression molding process.

Example 6 Degradation Testing

Biostability testing under strain was also carried out on varioussamples including PELLETHANE™ 80A, PELLETHANE™ 55D, ELASTEON E2A; andPIB-PU 80A. The composition of the PIB-PU 80A sample used in thisevaluation is shown below in Table 4.

TABLE 3 PIB-PU 80A PTMO HO—PIB—OH^(a) HO—PTMO—OH^(b) SS:HS wt % in ShoreA (wt % in SS) (wt % in SS) (wt:wt) polymer Hardness 80 20 65:35 13 80^(a)HO—PIB—OH, M_(n) = 2200 Da. ^(b)HO—PTMO—OH, M_(n) = 1000 Da.

In this test, the samples were subjected to accelerated metal ionoxidation and environmental stress cracking. To conduct the study, thesamples are strained to 150% and then left in the corrosive andoxidizing CoCl₂/H₂O₂ solution for 15 weeks at 50° C. under strain. Thesolutions were changed every other day to ensure a steady concentrationof radicals. The samples are removed from the solution every three weeksand tested for loss in mass (degradation); tensile loss, change inmolecular weight and surface erosion.

FIGS. 26 and 27 are bar graphs showing the loss in mass (degradation) at3 weeks and at 6 weeks. At 3 and 6 weeks, PELLETHANE™ 80A andPELLETHANE™ 55D showed the greatest average percent mass loss. At 3weeks ELASTEON E2A and the PIB-PU 80 sample showed a 0.74% and a 1.51%average loss in mass, respectively. At 6 weeks, ELASTEON E2A and thePIB-PU 80 samples showed approximately a 3% and a 4% average loss,respectively.

The tensile loss results for each of the samples at 3 weeks aresummarized in Table 3, presented below.

TABLE 4 Tensile Loss Ultimate % Spec. Break Tensile % Tensile PolymerNo. location Strength Elongation Loss P-80A  1 g 31 360  2 g 24 340  3 g32 360 AVG 29 354 56.06 P-55D 14 t 45 186 15 t 39.5 175 16 t 42 214 AVG42.17 192 15.67 E2A  5 t 29.2 438  6 g 14 242  7 g 26 387 AVG 27.6 413 8PIB—PU  9 t 21 280 10 g 26 304 11 g 23 345 12 g 31 380 AVG(10, 26.67 3438.05 11, 12)

PELLATHANE™ 80A exhibited approximately a 56% loss in tensile strengthafter 3 weeks. PELLATHANE™ 55D showed approximately a 16% loss intensile strength. The results for both ELASTEON E2A and PIB-PU 80 werecomparable. The ELASTEON E2A and PIB-PU 8-samples both showed an 8% lossof tensile strength.

The samples were also evaluated using ATR-FTIR. FIGS. 28-31 showrepresentative FTIR spectra taken at 0 weeks and 3 weeks for each sampleundergoing evaluation. Consistent with the previous testing results,discussed above, the spectra obtained for the PELLATHANE™ 80A andPELLATHANE™ 55D samples indicated the greatest amounts of degradationafter three weeks.

The samples were also evaluated using SEM. Comparative SEM photos ofeach of the samples were taken at 0 weeks and 3 weeks and are shown inFIG. 32. The PELLETHANE™ samples represented in the top two imagesshowed cracking and surface degradation at 3 weeks. The ELASTEON E2A andPIB-PU samples, represented in the third and fourth images,respectively, exhibited minimal surface degradation at 3 weeks.

Although various embodiments are specifically illustrated and describedherein, it will be appreciated that modifications and variations of thepresent invention are covered by the above teachings and are within thepurview of the appended claims without departing from the spirit andintended scope of the invention.

We claim:
 1. An implantable medical lead comprising: an elongated leadbody comprising a lumen, at least one conductor disposed within thelumen and at least one electrode operatively coupled to the conductorand disposed along the lead body, wherein the lead body has a Shorehardness from about 30A to about 75D and comprises a polyisobutyleneurethane, urea or urethane/urea copolymer comprising soft polymersegments and hard polymer segments; wherein the soft polymer segmentscomprise a polyisobutylene segment and at least one additional polymersegment comprising a residue of: a polyether diol, a fluorinatedpolyether diol, a fluoropolymer diol, a polyester diol, a polyacrylatediol, a polymethacrylate diol, a polysiloxane diol, a fluorinatedpolysiloxane diol, or a polycarbonate diol; and wherein a weight ratioof soft segments to hard segments in the copolymer ranges from 50:50 to90:10.
 2. The implantable medical lead according to claim 1, wherein aweight ratio of polyisobutylene to additional polymer ranges from about70:30 to about 90:10.
 3. The implantable medical lead according to claim1, wherein the soft segments comprise a polyisobutylene segment and aresidue of a polyether diol.
 4. The implantable medical lead accordingto claim 1, wherein the soft segments comprise a polyisobutylene segmentand a residue of a polyether diol, and wherein the polyether diolcomprises a polytetramethylene oxide diol.
 5. The implantable medicallead according to claim 4, wherein a weight ratio of polyisobutylene topolytetramethylene oxide diol ranges from about 70:30 to about 90:10. 6.The implantable medical lead according to claim 1, wherein thepolyisobutylene segment comprises a residue of a saturatedpolyisobutylene diol.
 7. The implantable medical lead of claim 1 whereinthe lead body comprises an inner lumen and an inner surface of the lumencomprises the copolymer.
 8. The implantable medical lead according toclaim 7, wherein the conductor is a coiled conductor having a co-radialconfiguration and wherein the inner surface is disposed over an outersurface of the coiled conductor.
 9. The implantable medical leadaccording to claim 1, wherein the lead body comprises an inner tubularlayer and an outer tubular layer, wherein at least one of the inner andouter tubular layers comprises a polyisobutylene urethane, urea orurethane/urea copolymer.
 10. The implantable medical lead according toclaim 9, wherein the lead comprises first and second coiled conductorshaving a co-axial configuration, wherein the inner tubular layer isdisposed between the first and the second conductors, and wherein theouter tubular layer is disposed over the second coiled conductor. 11.The implantable medical lead according to claim 1, wherein the lead bodycomprises a Shore hardness between about 30A and 100A.
 12. Animplantable medical lead comprising: an elongated lead body comprising alumen, at least one conductor disposed within the lumen and at least oneelectrode operatively coupled to the conductor and disposed along thelead body, wherein the lead body comprises a polyisobutylene urethane,urea or urethane/urea copolymer in each of a proximal region comprisinga first Shore hardness, a middle region comprising a second Shorehardness and a distal region comprising a third Shore hardness; whereinthe copolymer comprises soft polymer segments and hard polymer segmentsand wherein the soft polymer segments comprise a polyisobutylene segmentand at least one additional polymer segment comprising a residue of: apolyether diol, a fluorinated polyether diol, a fluoropolymer diol, apolyester diol, a polyacrylate diol, a polymethacrylate diol, apolysiloxane diol, a fluorinated polysiloxane diol, or a polycarbonatediol.
 13. The implantable medical lead according to claim 12, whereinthe distal region comprises a Shore hardness from about 30A to about70A.
 14. The implantable medical lead according to claim 12, wherein themiddle region comprises a Shore hardness from about 60A to about 85A.15. The implantable medical lead according to claim 12, wherein theproximal region comprises a Shore hardness from about 85A to about 100A.16. The implantable medical lead according to claim 12, wherein the leadbody further comprises one or more transition regions adjacent theproximal, middle or distal regions, and wherein transition regions havea different shore hardness than the adjacent proximal, middle or distalregion.
 17. The implantable medical lead according to claim 12, whereinthe soft segment in each region comprises a residue of a polyether dioland wherein the polyether diol comprises a polytetramethylene oxidediol.
 18. The implantable medical lead according to claim 17, wherein aweight ratio of polyisobutylene to polytetramethylene oxide in eachregion ranges from about 70:30 to about 90:10.
 19. The implantablemedical lead according to claim 12, wherein a weight ratio of softsegments to hard segments in the copolymer in each region ranges from50:50 to 90:10.
 20. The implantable medical lead according to claim 12,wherein the proximal region comprises a first weight ratio of softsegments to hard segments in the polyisobutylene urethane, urea orurethane/urea copolymer, the middle region comprises a second weightratio of soft segments to hard segments in the polyisobutylene urethane,urea or urethane/urea copolymer, and the distal region comprises a thirdweight ratio of soft segments to hard segments in the polyisobutyleneurethane, urea or urethane/urea copolymer.
 21. An implantable medicallead comprising: a flexible, elongated lead body comprising an innertubular member including at least one longitudinal lumen therethrough;at least one conductor extending through the at least one lumen of theinner tubular member, the conductor including an electrode having anexposed surface relative to the lead body; and at least one polymericcomponent connected to at least one of the lead body, conductor andelectrode, the at least one polymeric component comprising apolyisobutylene urethane, urea or urethane/urea copolymer, wherein thecopolymer comprises soft polymer segments and hard polymer segments andwherein the soft polymer segments comprise a polyisobutylene segment andat least one additional polymer segment comprising a residue of: apolyether diol, a fluorinated polyether diol, a fluoropolymer diol, apolyester diol, a polyacrylate diol, a polymethacrylate diol, apolysiloxane diol, a fluorinated polysiloxane diol, or a polycarbonatediol.
 22. The implantable medical lead according to claim 21, whereinthe at least one polymeric component comprises a lead terminal, terminalpin, a lead tip, O-ring, seal or a header.
 23. The implantable medicallead according to claim 21, wherein the at least one polymeric componentcomprises a thin film disposed on or adjacent to the exposed surface ofthe electrode.
 24. The implantable medical lead according to claim 23,wherein the thin film comprises a plurality of electrospun fiberscomprising the polyisobutylene urethane, urea or urethane/ureacopolymer.
 25. The implantable medical lead according to claim 23,wherein the thin film is disposed on a portion of the conductor.
 26. Theimplantable medical lead according to claim 21, wherein the at least onepolymeric component comprises a polymer tube disposed adjacent to theexposed surface of the electrode.